Effectiveness of a Polyphenol-Enriched Blend on Weight Management and Metabolic Syndrome-Related Parameters in Healthy Overweight Adults

Abstract

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study was to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts on weight management, body fat, appetite, lipid, and glucose profiles in an overweight population for 90 days. The volunteers presented significant weight loss in absence of diet (approximately 3 kg, −3.4% total body weight), which coincided with decreased body fat (−1.7%, equivalent to an almost 6% decrease compared to initial value). Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scans. Cholesterol levels were also significantly decreased (approximately 7% decrease). Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products as part of a healthy lifestyle.

1. Introduction

Excessive body fat causing overweight and obesity is a major pandemic this century, with over a third of adults affected worldwide [1,2,3]. When fat is stored in excess, over time it can cause numerous non-communicable diseases including high blood pressure, type 2 diabetes, fatty liver disease, heart disease, and cancer [4]. While there are numerous pharmaceuticals to treat obesity, these are not without important side effects. Therefore, discovering natural alternatives and taking preventive measures before the excess body weight progresses to further health complications is a growing trend [5].

To this end, plant polyphenols have been found to possess numerous health benefits, including anti-inflammatory, antioxidant, anti-lipogenic and anti-glycemic effects [6,7]. For example, plant extracts such as Hibiscus sabdariffa and Lippia citriodora have been found to be capable of modulating AMPK activation pathways [8,9]. Previous evidence has suggested that the activation of the energy sensor AMPK can be a therapeutic target for obesity. For example, AMPK activation can reduce LDL cholesterol and fatty acid synthesis [10,11]. Also, it can modulate lipid accumulation, reduce oxidative stress and block inflammatory adipokines [12,13]. In this sense, there are numerous studies, both preclinical and clinical, that have shown how the combination of these extracts can contribute to reducing body fat, which in turn causes weight loss [14,15,16,17,18,19,20,21,22]. A study performed in mice demonstrated that while both hibiscus and lemon verbena extracts, standardized in anthocyanins and verbascoside, respectively, were capable of increasing AMPK activation, the combination of these two further increased its activation over six-fold that of the individual extracts, suggesting a synergistic effect [16]. Furthermore, studies have revealed beneficial effects in lowering blood pressure, cholesterol and decreasing appetite, mainly by modulating the satiety-inducing hormone GLP-1.

However, the effects of the ingredient have been clinically tested only with a 500 mg daily dose. While the ingredient has been shown to be safe and effective at the dose used, there are several reasons that the use of a lower dose may be more favorable. For example, a higher dose would mean more capsules to take daily or a higher quantity of ingredient to add to the final formula, which can cause pill fatigue and patients to stop treatment before it is effective. Also, understanding the effects of the ingredient at different doses can allow for a more personalized approach to the treatment, where a specific dose can be recommended based on the patient’s objective with the product.

To this end, the objective of this study was to assess if this botanical blend may have certain benefits when taken at a lower dose, in this case 300 mg. The benefits in using a lower dose reside in reducing the number of capsules to take daily (and thus avoiding pill fatigue and therefore increasing compliance), while also providing a more personalized solution, as depending on the results of the study and the consumer’s expectations of the product, a specific dose may be recommended to the consumer.

2. Materials and Methods

2.1. Dietary Ingredient Description

A double-blind, placebo-controlled, randomized clinical study was conducted. The placebo group took 1 capsule per day comprising 300 mg each of excipient (microcrystalline cellulose). The experimental product contained a total of 300 mg of the botanical blend (which is under the umbrella of the trademark Metabolaid^® (Monteloeder S.L., Alicante, Spain)), comprised of lemon verbena and hibiscus extracts. The composition has been studied in previous reports [14,16]. Briefly, it is comprised of lemon verbena leaf extract, standardized in minimum 25% verbascoside, and hibiscus calyx extract, standardized in 10% anthocyanins. The participants were instructed to take the product 30 min before breakfast.

2.2. Study Design

A randomized clinical trial was carried out in which participants were assigned to two groups (placebo and experimental) to determine the effectiveness of a nutraceutical in reducing body weight and improving various health parameters (NCT05906771 in www.clinicaltrials.gov). Following published recommendations, subjects were electronically randomized using a two-arm block design (Figure 1).

2.3. Participants

A total of 61 participants, average age 41.7 ± 9.78 years, were recruited at a clinic in Elche, Alicante (Spain) during 2023. Of the total sample, 33 were men (42.6 ± 8.34 years) and 28 were women (41.1 ± 11.0 years). All were volunteers and were required to meet the following inclusion criteria: (1) adults, (2) overweight (body mass index 25–29.9 kg/m²), (3) non-medicated, and overall healthy. The exclusion criteria were: (1) pregnant or lactating subjects, (2) subjects who had participated in another study with similar characteristics in the last 3 months, (3) subjects with pathologies (e.g., diabetes), (4) consumption of drugs for weight loss, hypertension, or cholesterol, (5) subjects with food intolerances/allergies, (6) subjects not able to follow the intervention, (7) refusal to provide informed consent. Details on the participant’s biological parameters can be found in

Table 1. Average values of the study groups at the beginning of the study.

	Placebo	Experimental
Age (years)	40.99 ± 7.48	42.83 ± 7.39
Height (cm)	170.36 ± 7.60	171.99 ± 8.43
Weight (kg)	79.30 ± 7.21	81.06 ± 7.21
BMI (kg/m2)	27.16 ± 1.49	27.60 ± 1.35
Men/women ratio	17/14	16/14

cm = centimeters, kg = kilograms; m = meters.

. No significant differences were observed between groups at baseline.

2.4. Declarations: Ethical Approval, Consent to Participate and Consent to Publication

The present study was carried out in accordance with the standards of the Declaration of Helsinki. The Human Research Ethics Committee of the University of Alicante (Spain) granted approval to conduct a randomized trial (UA-2023-05-08) and all study participants gave written consent prior to participation. Additionally, the researchers maintained the confidentiality of all participants’ personal data, coding personal information for this purpose.

2.5. Intervention

The study was divided into several phases where specific variables were measured (Figure 2).

2.6. Study Variables

2.6.1. Satiety

Satiety was assessed using the visual analogue scale (VAS), a previously validated questionnaire [23,24] that was applied before, immediately after, and at the time of a standardized breakfast [25]. The satiety test was performed at four different times during the intervention period (initial visit, 30 days, 60 days and 90 days). To perform this test, participants were asked to arrive at the laboratory (in cases where attendance in person was not possible, a video call was used) in the morning after a 12 h overnight fast, and to refrain from alcohol consumption and intense physical activity for 24 h prior to the testing session. The standardized breakfast had an energy content of 616 kcal (2577.34) for men and 477 kcal (1995.77 kJ) for women [3]. For men, breakfast consisted of 200 mL of semi-skimmed milk or unsweetened soy drink, 100 g of whole grain bread with 6 g of oil, 50 g of chicken or turkey breast, 20 g of walnuts, and 200 g of apple. Macronutrient content comprised 82 g of carbohydrates, 19 g of fat, and 29 g of protein. For women, breakfast consisted of 200 mL of semi-skimmed milk, 60 g of whole grain bread with 3 g of oil, 40 g of chicken or turkey breast, 15 g of walnuts, and 200 g of apple. Macronutrient content was 65 g of carbohydrates, 15 g of fat, and 23 g of protein. All participants were instructed to consume the entire meal within 30 min. Before, immediately after, and 60 min after the standardized breakfast, participants were asked to record their appetite sensations using the visual analogue scale (VAS), evaluating their “desire to eat”, “hunger”, “fullness”, and “prospective food consumption”. Participants were asked to indicate on a scale from 0 to 10 how they felt at the time they answered these questions, for example, “How strong is your desire to eat?” (very weak—very strong). Subjects were asked to mark the line corresponding to their feelings at each moment. Figure 3 summarizes the VAS questions and the possible answers and ratings.

2.6.2. Blood Parameters

Blood samples were drawn and triglycerides, cholesterol, and glucose levels were assessed using an Accutrend^® Plus (Roche Diagnostics, Rotkreuz, Switzerland). The results were obtained in milligrams/deciliter (mg/dL). The Accutrend^® Plus test employs capillary serum and is based on the separation of blood cells through filtration with fiberglass when a blood drop is placed on the reactive strip. An enzymatic reaction within the strip occurs upon exposure to oxygen, resulting in a color change. The strip’s reflectance is measured at 660 nm, and the concentration of the various circulating parameters is determined using a straightforward algorithm. The accuracy of the Accutrend^® Plus, as stated in the product documentation, is 3.4% [26]. HbA1c was determined using A1cNow^®+ (Metrika, Inc., Sunnyvale, CA, USA). It has been determined that HbA1c measured with A1cNow InView is accurate, as shown by a correlation coefficient (r) of 0.96 [27].

2.6.3. Cardiovascular Parameters

At each visit, blood pressure was measured on one arm using an Omron RS2 (OMRON Healthcare, Mannheim, Germany) wrist blood pressure monitor. Participants were instructed to sit and unwind for 10 min before the measurement was taken. Measurements of both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were conducted during each assessment. The units of measurement are millimeters of mercury (mmHg).

2.6.4. Assessment of Body Composition and Anthropometry

In this project, the assessment of body composition was carried out using Tanita BC-730F, BIODY XPERT^ZM and bone densitometry (DXA). Weight was measured with the validated Tanita BC-730F bioimpedance scale (Amsterdam, The Netherlands). Participants came to the measurement wearing comfortable, loose clothing, avoiding clothing with zippers, belts or metal buttons. Objects such as keys or wallets that could be found in the area to be examined were removed. They were told that they could eat as usual but not to take calcium supplements in the 24 h prior to the examination.

Regarding anthropometric measurements, the data obtained from each subject were height, waist circumference, hip circumference and triceps skinfold. The standard protocol of the International Society for the Advancement of Kinanthropometry (ISAK) was followed [28]. The height of the subjects was measured with a SECA 123 stadiometer (Hamburg, Germany). From the body mass and height data, BMI (kg/m²) was calculated. Perimeters were measured with a Lufkin tape measure (accuracy 1 mm), and a Harpenden skinfold caliper (accuracy 0.2 mm) was used for skinfolds. The waist/hip ratio (WHR) was calculated from the waist and hip circumferences. The resulting values may indicate different levels of risk for the health conditions mentioned. In general, a higher WHR indicates a higher proportion of abdominal fat, also known as central or android obesity, which is associated with a higher risk of metabolic and cardiovascular problems.

2.7. Statistical Analysis

The statistical processing and analysis of the data was carried out using the JAMOVI statistical package. Initially, a principal component analysis was applied together with logistic regression and normality analysis, with the objective of identifying variables with the potential to influence the modification of health bio-parameters. Next, comparisons of means were made to evaluate the existence of significant differences between the groups at specific times: before, during, and after the intervention. An analysis of covariance (ANCOVA) (linear model; time × groups) was used to analyze the effects of the intervention on the results. Baseline variable results were included as covariantss as potential confounding factors. Statistical significance was set at p < 0.05 for all tests. The results are reported as means and standard deviation for each group. Additionally, the effect size was analyzed to provide a quantitative measure of the magnitude of the differences found.

Correlation analysis was performed using Pearson’s coefficient. This value was contrasted with the following hypothesis (using a 95% confidence coefficient): H0 (null hypothesis), there is no correlation between the two variables; H1 (alternative hypothesis), there is correlation between the variables. The p-value was calculated and values below 0.05 were determined to indicate a correlation between the variables. The correlation values ranged from −1 to 1, where negative values indicate an inverse correlation (when one variable increases, the other decreases) and positive values indicate a direct correlation (both variables increase or decrease). The closer the value to −1 or 1, the stronger the correlation.

3. Results

3.1. Satiety

Results of the satiety questionnaires performed can be found in

Table 2. Satiety questionnaire results. Data are presented as means ± SD.

		Placebo				Experimental
		Day 0	Day 30	Day 60	Day 90	Day 0	Day 30	Day 60	Day 90
Pre-Breakfast	How hungry do you feel?	5.71 ± 2.22	5.42 ± 2.53	4.83 ± 2.49	6.06 ± 2.29	5.8 ± 2.5	5.7 ± 2.22	5.89 ± 1.95	5.6 ± 2.11
	How full do you feel?	2.9 ± 1.83	3.03 ± 1.85	4.00 ± 2.26	3.32 ± 2.12	3.13 ± 2.05	3.83 ± 1.66	3.74 ± 2.05	4.17 ± 1.91 *
	How satisfied do you feel?	3.29 ± 1.88	3.65 ± 1.72	4.33 ± 2.25	3.58 ± 2.08	3.3 ± 2.05	3.83 ± 1.74	3.85 ± 2.05	4.23 ± 1.91
	How much could you eat now?	6.48 ± 2.14	6.35 ± 2.09	6.1 ± 2.34	6.55 ± 2.39	6.37 ± 2.13	6.17 ± 1.9	6.22 ± 1.95	5.67 ± 2.11
Post-Breakfast	How hungry do you feel?	0.52 ± 0.89	0.77 ± 1.09	0.4 ± 0.86	0.74 ± 1.12	1.1 ± 1.58	0.9 ± 1.4	0.59 ± 1.08	0.53 ± 1.01 ++
	How full do you feel?	9.06 ± 1.29	8.42 ± 1.84	8.83 ± 1.21	8.81 ± 1.22	8.33 ± 1.65	8.57 ± 1.28 +	9.15 ± 0.99 *++	9.07 ± 1.46 *+
	How satisfied do you feel?	9.19 ± 1.14	8.58 ± 2.08	8.83 ± 1.18	8.94 ± 1.12	8.67 ± 1.35	8.97 ± 1.25 +	9.41 ± 0.89 *+	9.13 ± 1.41
	How much could you eat now?	1.19 ± 2.2	1.45 ± 2.32	2.00 ± 2.64	1.84 ± 2.98	2.13 ± 2.34	1.87 ± 2.22	1.44 ± 2.19 ++	1.43 ± 2.51
1 h Post Breakfast	How hungry do you feel?	1.35 ± 1.5	1.42 ± 1.36	1.43 ± 1.22	1.81 ± 1.85	1.97 ± 1.71	1.43 ± 1.38	1.7 ± 2.03	0.83 ± 1.09 ***+
	How full do you feel?	7.52 ± 2.45	6.77 ± 2.35	7.63 ± 1.77	7.35 ± 1.84	7.9 ± 1.58	8.27 ± 1.64 ++	8.3 ± 1.51	8.47 ± 2.13 +
	How satisfied do you feel?	8.16 ± 1.68	7.65 ± 1.58	7.63 ± 1.79	7.52 ± 1.98	7.83 ± 1.66	8.30 ± 1.58 +	8.48 ± 1.72 +	8.8 ± 1.67 *+++
	How much could you eat now?	2.1 ± 1.89	2.68 ± 2.21	2.5 ± 1.78	2.77 ± 1.96	2.83 ± 2.26	2.43 ± 2.1	1.93 ± 1.52 ++	1.63 ± 1.56 *++

SD = standard deviation. Statistical significance: * = p < 0.05, *** = p < 0.005 vs. baseline, + = p < 0.05, ++ = p < 0.01, +++ = p < 0.005 vs. placebo.

. Briefly, no significant differences were reported before breakfast throughout the experimentation process, except for the question “How full do you feel?” In this case, the group consuming the experimental product presented a significantly higher value after 90 days of intake compared to baseline values. Therefore, this result suggests that the product does not reduce hunger in fasting conditions.

However, noticeable differences were observed between the two study groups after the set breakfast. Specifically, the experimental group scored significantly higher compared to baseline values on the questions “How full do you feel?” (at day 60 and 90) and “How satisfied do you feel?” (at day 60), when assessed immediately after breakfast. When the participants filled out the questionnaire 1 h after breakfast, more significant results appeared, not only with respect to baseline values but also with respect to the placebo group. For the questions “How hungry do you feel?” and “How much could you eat now?”, the experimental group reported significantly lower values compared to placebo at 90 and 60 days of treatment, respectively. A significantly higher value versus placebo was also detected at day 30 for the questions “How full do you feel?” and “How satisfied do you feel?”

Overall, these results would suggest that the ingredient has a significant effect on inducing satiety post-meal, but not in fasting conditions. These are similar results to those observed in previous studies, where it was also shown that this effect coincided with a significant increase in the levels of the satiety-inducing hormone GLP-1 in blood [13,18].

3.2. Blood Tests for Glucose, Cholesterol, and Triglycerides

Blood samples were taken from the volunteers at the beginning and end of the study. Cholesterol, triglycerides, and glucose were measured (Figure 4). As a result, a significant reduction was observed in the experimental group in total cholesterol levels. As for triglyceride levels, both study groups reported a decrease, with the placebo group reaching statistical significance and the experimental group revealing a trend. Finally, blood glucose and HbA1c levels remained unchanged, which was expected, as overall the volunteer’s levels were in the healthy range.

Therefore, it can be concluded that the experimental product contributes to lowering cholesterol levels, while glucose levels remain unchanged in normoglycemic individuals.

3.3. Blood Pressure and Heart Rate

Blood pressure and resting heart rate were analyzed at the beginning of the study and days 30, 60 and 90 (Figure 5). Interestingly, the placebo group revealed a slight but significant increase in blood pressure levels throughout the study compared to baseline values at day 30 and 60, with an increase in diastolic blood pressure observed at day 90. The group taking the experimental product, on the other hand, did not reveal such an increase, and this difference was statistically significant at days 30 and 60 with respect to systolic blood pressure. Resting heart rate did not change throughout the study (data not shown). Therefore, these results suggest that the ingredient does not alter the blood pressure levels in normotensive individuals.

3.4. Body Weight, Bioimpedance, and Anthropometry Assessment

Body weight, bioimpedance (using a Tanita), and anthropometric measurements were performed during each visit (Figure 6). Regarding body weight, the experimental product reduced body weight (−2.8 kg, approximately −3.4% of total body weight) after 90 days of treatment. This result is statistically significant compared to baseline values and placebo throughout the whole study period.

As for fat mass, significant reductions, both compared to baseline and placebo, were observed in total body fat mass (−1.7%, equivalent to −5.7% vs baseline) at 90 days, and visceral fat (−0.65%, equivalent to −8.2% vs baseline) at 60 and 90 days.

Waist circumference analysis revealed a significant reduction at days 60 and 90, whereas no significant changes in hip circumference were detected. Triceps skinfolds also revealed a significant reduction after days 30 (vs. placebo) and 90 (vs. baseline and placebo).

Therefore, these studies suggest that the experimental product contributes to lowering body weight in absence of diet. Furthermore, the main reason behind this weight loss is the reduction in fat mass, visceral fat being the most relevant area of body fat loss, as confirmed through the skinfold analysis.

3.5. Bioimpedance (BIODY XPERTZM) Assay

Electrical bioimpedance analysis with the BIODY XPERT^ZM was performed at days 0, 30, 60 and 90 (Figure 7). Compared to baseline, the experimental group showed reduced fat mass (−4.1%) throughout the whole study, being statistically significant versus baseline at days 30 and 90, and versus placebo at days 60 and 90. Muscle mass remained unchanged, while slight but significantly lower water mass was observed at day 30 and 90.

Therefore, it can be concluded that the ingredient contributes to lowering body fat mass after 90 days of intake while maintaining muscle mass, with a slight reduction in water mass observed.

3.6. DEXA Scan

This test was performed at the beginning and end of the study. Bone, upper body fat, total fat and muscle mass were assessed (Figure 8). Compared to baseline, the placebo group revealed a significant increase in upper body and total fat mass. On the other hand, the experimental group showed significantly reduced upper body fat mass (−1.6 kg, −9.9% vs. baseline values) and total fat mass (−2.4 kg, −8.2% vs. baseline values) at day 90. These differences were statistically significant compared to baseline values and placebo. No changes in muscle or bone mass were observed.

Therefore, the results indicate that the botanical blend contributes to lowering body fat mass in absence of diet. These results also corroborate those observed by the skinfold assessment, where the upper body area is where the most of fat loss was observed.

3.7. Correlation Analysis

A correlation analysis was performed to assess how the biological parameters measured behaved with respect to each other (Figure 9). The most noticeable differences were observed with body weight, where a stronger correlation was detected between body weight and several of the satiety questions. For example, a slightly negative correlation was detected in the placebo group between body weight and the question “How hungry do you feel?” immediately after breakfast as well as 1 h afterwards, whereas a strong positive correlation was detected in the experimental group. This could be interpreted in the case of the placebo group that less body weight correlated with more hunger after the meal, while in the experimental group, less body weight correlated with less hunger after breakfast. Similar results were observed regarding the questions “How satisfied do you feel?” and “How much could you eat now?” In these cases, a stronger negative correlation was detected in the experimental group compared to the placebo. Overall, this could suggest that in the experimental group, those losing more weight equally felt less hungry after the meals, and therefore a stronger satiety effect (due to the product’s effect) was perceived by the subjects.

3.8. Subgroup Analysis Based on Gender

Statistical analysis based on gender differences were also performed (see Appendix A). Overall, the results were similar in both cases, although certain statistically significant improvements seemed to appear in women earlier in the study than men.

4. Discussion

In the current study, we have demonstrated that a single daily intake of 300 mg of a botanical blend (under the trademark name Metabolaid^®) can contribute to help lose body weight through the loss of fat mass, especially in the upper body region, after 90 days, with significant results observed as early as during the first month of treatment. Also, the subjects reported higher levels of satiety, especially post-meal. Lastly, a reduction in cholesterol levels was observed.

Overall, the subjects taking the experimental product lost an average of almost 3 kg after 3 months, which was approximately 3.5% of their total body weight. When analyzing body fat mass by DEXA scan, around 2.5 kg of body fat was lost, while no changes in muscle or bone mass were observed. Water content also remained unchanged. Therefore, it can be concluded that the vast majority of the body weight lost was due to fat mass loss. When analyzing localized fat, it was observed that upper body fat mass was the location where the most fat was lost (approximately 10% upper body fat loss compared to baseline values). These results are in absence of diet or exercise.

An interesting observation that has been assessed in previous studies is the effect of the ingredient on satiety [15,20]. In the present study, the participants were instructed to consume a set breakfast within 30 min. A validated VAS questionnaire was used, where the participants answered the same questions before, immediately after and 1 h after the breakfast. The questions were How hungry do you feel?, How full do you feel?, How satisfied do you feel?, and How much could you eat right now? Based on these questions, the most noticeable results were observed in the experimental study group in the questions answered after breakfast, both immediately and 60 min afterwards. The most significant answers in the after breakfast questions were to How full do you feel? and How satisfied do you feel? This suggests that the ingredient has a noticeable effect in managing appetite during and after a meal, with less noticeable effect in fasting conditions (although significant effects were observed after 90 days). These effects were also noticeable 1 h after breakfast. Therefore, the observed weight loss could be due to not only the direct effect of the ingredient on AMPK activation and fat metabolism but also on appetite management.

Other less noticeable results were observed in blood markers and blood pressure. Specifically, a slight but significant reduction in cholesterol was observed. Systolic blood pressure was also significantly lowered. However, in these cases, the reduction was very low, and may possibly be due to the decreased body weight loss, and not so much the direct effect of the ingredient.

This evidence is similar to the results observed in previous publications [14,15,16,17,18,19,20,21,22], although in those studies, a 500 mg daily dose was provided. With respect to the previous publications, the major differences reside in the lack of response in blood pressure and glycemic marker levels, and that overall, the results are not as remarkable (up to twice as much body weight loss was observed in previous studies, for example). Despite this, there are numerous advantages for the use of a lower dose. First of all, a 500 mg dose means that the product must be taken in at least two capsules, as opposed to 300 mg, which fits in a single one. Pill fatigue is a matter of concern, with over half of patients not adhering adequately to long-term treatments [29]. This is even more pronounced in the case of dietary supplements and can have deleterious effects in cases where there exists a severe condition that can be accompanied by a nutritional deficit [30,31,32,33]. Regarding weight management treatments, lifestyle interventions have been shown to be beneficial for weight loss [34], although in most cases, the lost weight is eventually regained [35]. Therefore, finding methods to increase adherence, such as reducing the number of capsules to take, can have longer-lasting benefits.

Similarly, the possibility of using more innovative final product formats, such as gummies, gels or drinks, can also facilitate adherence [36]. However, these formats have additional technical challenges, such as ingredient stability, solubility, and organoleptic. This is particularly true in the case of botanicals. In this regard, the botanical blend has been tested in gummy formats and drinks, and while the ingredient was found to be stable and soluble, it presented certain organoleptic challenges. Also, a 500 mg daily dose requires having to divide the dose into at least three gummies, which can be too high. Therefore, the possibility of using a lower dose, while retaining to a certain point its functional benefits, can be advantageous for its use in these end formats.

Besides the differences regarding dose, the current study presents additional insights on the product’s effects that have not been addressed in previous studies. For example, satiety assessment was performed in this case at different intervals of the study, while in previous reports, this was conducted only at the beginning and end of the trial [15,20]. As a result, it was observed that the product’s effect on satiety can be perceived by the participants as early as 30 days post-meal. This information provides further proof that the product’s effect resides in the signaling pathway that is activated when eating. Previous studies suggested that this was at least partly due to increased GLP-1 expression [15,20], which is a known satiety-inducing hormone, and that the gut microbiome plays an important role [37]. Our investigations have also elucidated on the potential gut microbiome-modulating effects of the ingredient, increasing short-chain fatty acid production, particularly butyrate, while increasing the population of several bacterial populations that are implicated in obesity and type 2 diabetes, such as Akkermansia, Prevotella, or Blautia [22,38].

In addition, the current study has revealed that under normoglycemic and normotensive conditions, the product does not have any significant effect. This is especially relevant, as there are concerns regarding the effect of certain dietary supplements that may have blood pressure- or glucose-lowering effects, which in healthy individuals could potentially lower their levels to hypotensive or hypoglycemic levels. In the current study, no such effect was observed, proving that the product is safe for these individuals.

Lastly, this is the first study conducted with the ingredient that has provided a complete comparative analysis of body composition using anthropometry, bioimpedance, and DEXA scan. While this may seem redundant, it provides proof of the robustness of the evidence observed with the botanical blend on body fat mass loss. Significant reductions were observed in all three assessments, with special emphasis on the reduction in the upper body/visceral fat mass. Therefore, the study provides additional supporting evidence on the effect of the product in reducing body weight mainly by targeting visceral body fat, while muscle, bone, and water mass are largely unaffected.

Limitations of the current study include the duration of the study (3 months). While this is a standard duration in many intervention studies of this kind, it does not allow elucidation on the effectiveness of the ingredient in the long term. Also, a larger study population would have allowed assessment of possible statistical differences in the biological parameters analyzed based on gender.

5. Conclusions

The current study reveals that the daily consumption of 300 mg of a blend comprised of lemon verbena and hibiscus extracts standardized in verbascoside and anthocyanins, respectively, can help reduce over 3.4% of total body weight in three months in absence of diet and exercise. The study also revealed that the majority of the weight loss was due to body fat loss (with over 6% body fat loss in 3 months), with a more significant effect in the fat located in the abdominal region. Part of the weight loss observed was due to increased perceived satiety, especially after meals. No muscle or significant water loss was observed. Other additional benefits included lowering blood cholesterol, while glucose and blood pressure, which were initially in the healthy range, remained unchanged. Based on the evidence presented here and that observed in previous studies, it can be concluded that a 300 mg daily dose may help reduce appetite and body weight, albeit at a slower rate than the 500 mg dose. Further studies are necessary to assess the potential blood pressure-, cholesterol-, and glucose-lowering effects of the blend at the lower dose.