A 12-week, double-blind, quasi-randomized, placebo-controlled study to evaluate the efficacy and safety of Coleus forskohlii (Forcslim) on body weight loss

Abstract

Background

Overweight and obesity have emerged as a global epidemic, significantly impacting human health. Traditional usage and growing scientific evidence suggest that Coleus forskohlii extract (Forcslim) may aid in reducing excess body weight and fat. This study aimed to evaluate the efficacy and safety of Forcslim supplementation in overweight individuals.

Methods

A quasi-randomized, double-blind, placebo-controlled clinical trial was conducted in 60 overweight subjects aged 20–70 years over a period of 12 weeks. The participants were assigned to receive either Forcslim or placebo. The key outcome measures included body weight, body mass index (BMI), body composition, and anthropometric parameters. Additionally, lipid profile parameters and safety markers (including metabolic, hepatic, and cardiovascular indicators) were assessed throughout the study duration.

Results

Compared to the placebo group, the Forcslim group showed significant reductions in waist circumference (−1.83 cm; p < 0.01) and body weight (−1.93 kg; p < 0.001). Significant improvements in anthropometric parameters were observed exclusively in the Forcslim group. Furthermore, triglyceride (TG) levels were significantly reduced (p < 0.01), while high-density lipoprotein (HDL) levels showed a significant increase (p = 0.001). No clinically significant changes were observed in metabolic markers, liver and muscle enzyme levels, heart rate, blood pressure, or reported adverse effects, indicating a favorable safety profile.

Conclusions

Forcslim demonstrated significant anti-obesity effects, including reductions in body weight, waist circumference, and improvements in the lipid profile. These findings suggest that C. forskohlii extract supplementation may serve as a safe and effective alternative to synthetic anti-obesity drugs.

1. Introduction

Obesity is a complex health and global epidemic issue covering different age groups and it affects more than 16% of the adult population. The disease poses a serious threat to worldwide public health and is defined by a body mass index (BMI) of 30 kg/m² or higher [1]. Obesity raises morbidity and mortality and is related to type 2 diabetes, cancer, stroke, as well as cardiac problems [2]. According to WHO estimates, being overweight or obese would cause 1.9 billion people and children to lose their health by 2035 [3]. The relationship between obesity and metabolic disorders has been the subject of extensive research, with particular attention given to the role of adipose tissue as an endocrine organ that is metabolically active [4]. From the perspective of personalized medicine, the lack of effective treatments for obesity necessitates the creation of customized strategies. Although most synthetic anti-obesity medications have demonstrated efficacy in promoting weight loss, their use is often limited by high cost, the potential for abuse or misuse, and the occurrence of undesirable side effects. These limitations may stem from an incomplete understanding of their mechanisms of action and safety profiles of the chemical constituents involved [5,6]. In contrast, surgical interventions for obesity are associated with several complications, including malnutrition, anemia, thrombosis, and infection, which are frequently observed in severely obese patients undergoing such procedures [7]. Therefore, there is an urgent need to identify safer and more effective alternative strategies for obesity management. Plant-based medications play a vital role in maintaining health by preventing and treating various diseases and their associated complications [8]. In particular, polyherbal formulations may exert enhanced anti-obesity effects through synergistic interactions, enabling the modulation of multiple biological targets. Moreover, these herbal preparations often confer additional health benefits beyond weight management, supporting their potential as holistic therapeutic options [9–11]. Natural products are appealing sources for anti-obesity agents, because many of them can alter host metabolic processes and maintain glucose homeostasis through metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancement, abiogenesis inhibition, and adipocyte apoptosis induction [12–14].

Coleus forskohlii is an Indian plant that has long been used in traditional Indian medicine (Ayurveda) [15,16]. C. forskohlii belongs to the family Labiatae (Lamiaceae), which is commonly known as the mint family. The plant is rich in various alkaloids, with the root portion being a primary source of forskolin, a biologically active compound. Forskolin is a diterpene that directly activates adenylatecyclase [17], an enzyme responsible for the production of cyclic adenosine monophosphate (cAMP) within cells. cAMP plays a key role in promoting the breakdown of stored fats in animal and human adipocytes [18]. It regulates the body's thermogenic response to food, increases the basal metabolic rate, and enhances the utilization of body fat as an energy source. Additionally, cAMP facilitates the release of fatty acids from adipose tissue, leading to increased thermogenesis, a reduction in body fat, and a theoretical increase in lean body mass [19]. Forskolin elevates intracellular cAMP levels, thereby stimulating lipolysis; higher concentrations of forskolin result in greater cAMP accumulation and enhanced lipolytic activity [18]. Increased lipolysis promotes fat degradation and the use of fat as fuel [17], which may support fat and weight loss. Supplementation with forskolin is therefore thought to enhance fat loss without concomitant loss of muscle mass [20]. This study aimed to assess the impact of a 12-week C. forskohlii supplementation regimen on body fat composition in individuals with obesity, employing a quasi-randomized, double-blind, placebo-controlled design.

2. Materials and methods

2.1. Study products

Forcslim was prepared by Star Hi Herbs Pvt. Ltd., Jigani, Bangalore, Karnataka, India. The investigational product and placebo were administered in the form of solid gelatin capsules. Each test capsule contained 250 mg of 10% ethanolic CF extract and excipients, while the placebo contained croscarmellose sodium. The participants were instructed to consume one capsule of the investigational product or placebo twice daily, 30 min before major meals, for a duration of 12 weeks.

2.2. Study design

The study & Research Centre, B.G. Nagara, Mandya, Karnataka, India. The protocol was approved was a quasi-randomized, double-blind, placebo controlled 12-week, prospective, parallel group trial conducted at the Institutional Ethics Committee of AH&RC, Adichunchanagiri Hospital by the institutional review board of the hospital (IEC/AHRC/CT/004/2022). Based on the predefined inclusion and exclusion criteria, subjects who successfully passed the screening test were enrolled in the study. Among the applicants who volunteered to participate, 60 adults were selected after obtaining written informed consent. Prior to randomization, all participants underwent baseline evaluation, which included measurement of anthropometric parameters such as body weight, height, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio (WR). In addition, blood pressure and heart rate were recorded, and blood samples were collected for biochemical analysis. The participants were allocated into two groups using a quasi-randomized method: Group A received Forcslim (n = 30), and Group B received a placebo (n = 30). The blood parameter results were concealed from both the investigators and the participants until completion of the statistical analysis (Figure 1). The sample size of 60 patients was decided based on a review of the literature on studies with C. forskohlii.

Figure 1.

Flowchart for the study subjects. Forcslim and Placebo were Randomized and analyzed.

During the run-in phase and throughout the study period, participants were instructed to maintain their usual diet and physical activity levels. All participants were required to maintain a food intake diary, which was submitted every four weeks. Anthropometric measurements, biochemical parameters, and appetite assessments were recorded at baseline (week 1) and subsequently repeated at weeks 4, 8, and 12 of the study.

During each visit, participants were asked to report any adverse events or unwanted side effects. In the case of serious adverse events, the participants were instructed to immediately notify the Principal Investigator (PJ) or the study team and visit the hospital for further evaluation.

2.3. Study participants

Subjects were adults (50 female and 10 male) aged 20–70 years with a body mass index (BMI) ≥ 25 kg/m² and waist circumference >94 cm (male) or <80 cm (female) without any comorbidities. Participants who had not received any other weight-control therapy within the previous 3 months were recruited through the internet. All eligible subjects who were in good health, as confirmed by their medical history, physical examination, and routine laboratory tests, and who provided written informed consent were enrolled in the study. The inclusion and exclusion criteria are listed in detail in Table 1.

Table 1.

Inclusion and exclusion criteria for selection of study participants.

Inclusion criteria

Gender: male and female Age: 20–70 years Body mass index: >25 kg/m2 Waist circumference: >94 cm for males or >80 cm for females

Exclusion criteria

Blood pressure ≥160/100 mmHg Diabetes defined by fasting blood glucose ≥126 mg/dL or random blood glucose ≥200 mg/dL or treated with oral hypoglycemic agents or insulin History of acute or chronic liver, kidney, or heart disease Allergic disease including bronchial asthma Significant musculoskeletal diseases that can interfere with exercise Alcohol or drug abuse Pregnant and lactating mothers Patients who were taking medications for weight loss, hypertension, or thrombocytopenia Participation in a weight loss program 3 months prior to the study start

2.4. Anthropometric and physiological measurements

All anthropometric measurements, including weight, height, waist circumference, and hip circumference, as well as physiological parameters such as blood pressure (BPO) and heart rate (HR), were measured using standard techniques and calibrated equipment [21]. Body mass index (BMI) was calculated using the formula: BMI (kg/m) = weight (kg)/height² (m). Waist-to-hip ratio (WR) was calculated as the waist circumference (cm) divided by the hip circumference (cm). Blood pressure and heart rate were measured using an automated digital BP monitor (Omron Healthcare, Kyoto, Japan) after the participant had been seated and relaxed for at least five minutes. All the measurements were performed in duplicate, and the mean of the two readings was considered as the final value.

2.5. Biochemical analysis

Aside from the anthropometric measures, 12 h fasting blood glucose and other biochemical analysis including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total protein, albumin, total bilirubin, AST (GOAT), ALT (GPT) and ALP, were performed. Alteration in liver function was assessed to study the effect on the liver at baseline and 12th week of the study. Alterations in blood lipids, and blood glucose will be measured on a fortnight basis along with the change in appetite.

2.6. Dietary intake assessment

Subjects recorded all food and fluid intake using dietary record forms. Dietary intake was subsequently analyzed using Food Processor III Nutrition Software (Version 7.5).

2.7. Appetite assessment

2.7.1. Appetite scale

Appetite was assessed using a visual analogue scale (VAS) ranging from high to low [14]. The large scale was used to evaluate subjective sensations related to appetite, including hunger, fullness, satiety, glucose levels, and perceived quality of food intake.

2.8. Safety assessment

The following procedures were performed to the safety of the extract: hematology and laboratory tests were conducted during screening, at baseline (0-week) and 12 week intervention periods for white blood cell (WBC), red blood cell (RBC), and platelet counts, hemoglobin, hematocrit, total protein, albumin, alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and creatinine levels. Electrocardiogram (ECG) was performed on the initial and final visit, where, pulse rate (PR) and blood pressure (BP) were measured during each visit. All participants were monitored for abnormal events at visit.

2.9. Data management and statistical analysis

The descriptive statistics were performed, and the data was presented as frequency with percentages and mean with standard deviation in case of categorical variable and continuous variable, respectively. Independent t-tests were conducted to assess all baseline outcomes between groups and paired (student) test was performed to compare the effect of the intervention before and after the treatment in both groups. A mixed model analysis of variance (ANOVA) was performed to examine the effects of the intervention (groups), time (week), and the interaction between the intervention and time using pairwise comparisons (Bonferroni's post-hoc test was used to account for multiple comparisons). A probability of less than 5% (p = 0.5) was considered to be statistically significant. All the analyses were performed using the Statistical Package for Social Sciences (SPSS; version 20).

3. Results

3.1. Demographic details

A total of 60 participants (Intervention: 30; Placebo: 30) were included and completed the study, including 50 (Intervention: 25; Placebo: 25) female and 10 (Intervention: 5; Placebo: 5) female. There was no significant (p < 0.05) difference in baseline characteristics between the arbitration and placebo groups including age, height, weight, BMI, waist circumference, hip circumference, and weight-hip ratio. The details are provided in Table 2.

Table 2.

Demographic characteristics of the study participants Forcslim and Placebo groups.

Variables	Forcslim group (n = 30)	Placebo group (n = 30)	p-value
Age (years)	39.80 ± 11.67	38.43 ± 10.81	0.676
Height (m)	161.17 ± 3.69	162.07 ± 3.78	0.706
Weight (Kg)	75.63 ± 5.01	758.3 ± 5.86	0.281
Body mass index (Kg/m2)	28.75 ± 1.45	28.62 ± 1.41	0.748
Waist circumference (cm)	90.50 ± 7.37	88.87 ± 7.23	0.985
Hip circumference (cm)	102.90 ± 5.95	101.07 ± 56.9	0.534
Waist hip ratio	0.87 ± 0.03	0.88 ± 0.04	0.406

Values are expressed as mean standard deviation (SD), n = number of participants.

3.2. ​​​Anthropometric and physiological parameters

The baseline, week 4, week 8, and week 12 anthropometric and metabolic parameters of the participants in the intervention and placebo group are provided in Table 3. A significant time effect (p < 0.01) between week 12 and the baseline was observed in weight, waist circumference, hip circumference, waist-to-hip ratio, total cholesterol, triglycerides, HDL, and heart rate, whereas time effects were not observed for other factors. Forcslim showed an 11.44% decrease in the atherogenic index compared to the placebo group (9.47%). Supplementation with the (Forcslim) for 12 week significantly (p > 0.01) reduced the weight, waist circumference, hip circumference, and weight-height ratio concentration compared with the placebo group. The outcomes and reports are provided in Table 3.

Table 3.

The demographic and metabolic markers from baseline to 12 weeks in the Forcslim and Placebo groups.

Variables	Study group	Baseline (pre)	Week 4	Week 8	Week 12 (post)	Pre-post difference (SEM, p-value)	Pair-wise comparison (MD; p-value)	Post-hoc analysis (F-value; p-value) Time interaction
Weight (kg)	Forcslim Placebo	75.63 ± 5.01 75.83 ± 5.86	75.00 ± 4.81 75.43 ± 5.57	74.30 ± 4.73 75.07 ± 5.57	73.70 ± 4.65 74.80 ± 10.44	0.18; 0.000* 0.17; 0.000*	0.625; 0.644	1.90.84; 0.006 2.8.45; 0.000*
Waist circumference (cm)	Forcslim Placebo	90.50 ± 7.37 88.87 ± 7.23	90.20 ± 7.55 88.83 ± 7.25	89.33 ± 7.61 88.43 ± 7.25	88.6747.33 87.9047.15	0.15; 0.000* 0.15; 0.000*	1.167; 0.540	1.101.67; 0.005* 2.10.12; 0.000*
Hip circumference (cm)	Forcslim Placebo	102.90 ± 59.5 101.07 ± 5.69	102.73 ± 6.08 101.00 ± 5.57	102.07 ± 6.19 100.50 ± 5.86	101.4745.95 100.4045.72	0.22; 0.000* 0.15; 0.000*	1.115; 0.310	1.44.34; 0.003* 2.5.24; 0.007*
Waist hip ratio	Forcslim Placebo	0.87 ± 0.03 0.88 ± 0.04	0.88 ± 0.028 0.88 ± 0.036	0.87 ± 0.030 0.88 ± 0.036	0.8740.028 0.8740.033	0.00; 0.000* 0.00; 0.000*	0.003; 0.740	1.16.96; 0.006* 2.3.58; 0.022*
RBS (mg/dL)	Forcslim Placebo	102.97 ± 21.20 97.73 ± 29.28	103.20 ± 20.86 98.17 ± 28.24	102.50 ± 20.18 97.27 ± 27.70	1015.3426.85 98.67420.65	0.96; 0.146 2.07; 0.656	4.592; 0.468	1.0.326; 0.7I7 2.0.918; 0.400
Total cholesterol (mg/dL)	Forcslim Placebo	194.80 ± 31.57 205.93 ± 35.8	191.20 ± 31.10 203.20 ± 35.38	187.63 ± 30.29 196.27 ± 47.99	183.57431.39 195.97435.69	0.51; 0.000* 0.75; 0.000*	11.042; 0.220	1.19.00; 0.000 2.0.580; 0.468
Triglycerides (mg/dL)	Forcslim Placebo	178.67 ± 29.18 187.40 ± 45.85	174.67 ± 28.55 183.97 ± 45.61	171.13 ± 29.51 177.13 ± 43.05	166.97429.66 176.77446.52	0.54; 0.000* 0.25; 0.000*	8.458; 0.388	1.35.35; 0.000 2.0.999; 0.330
HDL (mg/dL)	Forcslim Placebo	35.23 ± 5.27 39.50 ± l 1.99	37.07 ± 5.I9 4 O.2O ± 1I.3O	37.87 ± 5.03 43.23 ± 14.36	37.4344.63 41.13411.14	0.59; 0.001* 0.32; 0.000*	4.117; 0.075	1.7.43; 0.003* 2.0.959; 0.364
Systolic BP (mmHg)	Forcslim Placebo	122.33 ± 7.55 122.93 ± 9.19	123.23 ± 4.21 124.00 ± 5.22	123.73 ± 3.31 124.27 ± 3.67	123.6043.87 124.6744.15	1.49; 0.402 1.59; 0.286	0.742; 0.456	1.1.31; 0.272 2.0.04; 0.945
Diastolic BP (mmHg)	Forcslim Placebo	81.13 ± 5.52 80.66 ± 5.97	81.67 ± 3.79 82.60 ± 4.00	81.20 ± 2.71 80.87^2.08	80.9342.56 80,5342.10	1.08; 0.854 1.06; 0.901	0.067; 0.917	1. 2.047; 0.127 2.0.569; 0.589
Heartrate (bpm)	Forcslim Placebo	83.13 ± 4.06 82.60 ± 5.44	79.27 ± 4.41 78.87 ± 4.26	78.20 ± 3.66 78.2743.31	77.5344.29 77.2743.30	0.96; 0.000* 1.08; 0.000*	0.267; 0.736	1.32.039; 0.000 2.0.113; 0.934

The values presented as mean ± standard deviation; pre-post analysis based on the paired t-test; pairwise comparison and post-hoc analysis results based on the multiple comparisons as per Bonferroni (ANOVA).

Abbreviations: ALP: alkaline phosphatase; MD: mean difference; LDL: low-density lipoprotein; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; TB: total bilirubin; TP: total protein.

*indicates the significant difference (p < 0.05).

3.3. Effect of intervention on laboratory parameters

A significant time effect (p < 0.05) was observed for LDL, TOB, SGOT, and SGPT, whereas time effects were not observed for other factors. The pair-wise comparison indicated a significant group effect (p > 0.045) on total protein (Table 4). There was no significant group effect in all other parameters. The outcomes are presented in Table 4.

Table 4.

Selected hematological markers for the Forcslim and Placebo groups.

Variables	Study group	Baseline (pre)	Week 12 (post)	Pre-post difference (MD, p-value)	Pair-wise comparison (MD; p-value)	Post-hoc analysis (F-value; p-value) Time Interaction
LDL (mg/dL)	Forcslim Placebo	95.57 ± 24.60 99.47 ± 26.06	94.03 ± 21.61 101.00 ± 25.58	1.11; 0.180 2.13; 0.478	5.43; 0.386	1. 0.000; 0.001* 2. 1.624; 0.208
TB (mg/dL)	Forcslim Placebo	0.77 ± 0.26 0.84 ± 0.28	0.78 ± 0.26 0.84 ± 0.25	0.02; 0.798 0.04; 0.938	0.068; 0.289	1. 0.041; 0.001* 2. 0.005; 0.947
TP (g/dL)	Forcslim Placebo	7.16 ± 0.57 6.77 ± 0.93	7.16 ± 0.52 6.76 ± 0.88	0.05; 0.945 0.03; 0.677	0.392; 0.045*	1. 0.083; 0.774 2. 0.030; 0.863
Albumin (g/dL)	Forcslim Placebo	4.31 ± 0.44 4.09 ± 0.48	4.32 ± 0.49 4.16 ± 0.44	0.04; 0.715 0.03; 0.074	0.187; 0.120	1. 2.462; 0.122 2. 1.094; 0.300
SGOT (U/L)	Forcslim Placebo	28.27 ± 3.61 27.17 ± 5.22	29.10 ± 3.30 28.17 ± 4.45	0.30; 0.009* 0.75; 0.195	1.017; 0.318	1. 5.111; 0.028* 2. 0.042; 0.838
SGPT (U/L)	Forcslim Placebo	26.03 ± 6.17 23.97 ± 5.70	27.77 ± 5.36 26.93 ± 4.37	0.50; 0.002* 0.58; 0.000*	1.450; 0.288	1. 37.769; 0.000* 2. 2.601; 0.112
ALP (U/L)	Forcslim Placebo	97.23 ± 27.43 99.83 ± 26.66	97.70 ± 28.27 98.53 ± 23.81	2. 23; 0.836 2.47; 0.603	1.717; 0.798	1. 0.063; 0.803 2. 0.282; 0.598

The values presented as mean ± standard deviation; pre-post analysis based on the paired t-test; pairwise comparison and post-hoc analysis results based on the multiple comparisons as per Bonferroni (ANOVA).

Abbreviations: ALP: alkaline phosphatase; MD: mean difference; LDL: low-density lipoprotein; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; TB: total bilirubin; TP: total protein.

*indicates the significant difference (p < 0.05).

3.4. ​​​Safety assessment results

In order to test product safety, we looked for changes in liver function indices after product ingestion. In both groups, there were no significant changes in these indices that were within the normal ranges. All safety parameters were within normal ranges at baseline and at the end of the study in both groups (data not shown). These tests included blood pressure, ECG, liver, and renal function tests, and hematologic tests. No adverse events were reported during the study Table 4.

3.5. Dietary intake

The results from the food diary analyses at baseline and at weeks 4, 8 and 12 are shown in Table 5. The subjects participating in the study recorded all food and fluid intake during week 0 and month 12 of the testing sessions. Significant reductions in carbohydrate, fat, and total energy intake were observed over time in both groups. However, no significant differences were found between the Forcslim and placebo groups, suggesting that supplementation had no significant effect on dietary intake. The reductions observed over time may reflect participants' conscious efforts to reduce food consumption in order to support the weight loss process. It is possible that greater differences between groups might have been detected if a standardized dietary regimen had been implemented in the study. Such dietary control would allow the specific effects of supplementation to be monitored more accurately. Furthermore, physical activity levels were monitored throughout the study and remained stable across both groups, confirming that the observed differences in body composition were attributable to supplementation rather than changes in activity patterns.

Table 5.

Four-day total dietary intake for the Forcslim and Placebo groups.

Variable	Group	Week 0 (T1)	Week 8 (T3)	Week 12 (T4)	Significance
Protein (g/kg/d)	Forcslim Placebo	274.8 ± 118.0 302.5 ± 178.5	260.8 ± 84.0 280.7 ± 120.9	252.8 ± 60.5 262.1 ± 42.6	Group Time Group × Time	0.519 0.210 0.821
Fat (g/kg/d	Forcslim Placebo	275.3 ± 42.5 323.6 ± 105.8	233.2 ± 48.0 308.1 ± 79.1	184.0 ± 50.2 213.0 ± 56.4	Group Time Group × Time	0.143 0.002 0.686
Energy intake (kcal/kg/d)	Forcslim Placebo	7568 ± 1730 8297 ± 2510	6734 ± 1225 7872 ± 2260	5750 ± 1850 6595 ± 1570	Group Time Group × Time	0.288 0.009 0.912
Carbohydrates (g/kg/d)	Forcslim Placebo	889.3 ± 178.4 889.3 ± 154.7	883.5 ± 184.3 882.3 ± 215.4	830.5 ± 320.2 828.5 ± 174.5	Group Time Group × Time	0.729 0.024 0.656

3.6. Appetite analysis

An appetite inventory was used to evaluate appetite-related variables during each of the four testing sessions conducted in the study. The inventory assessed parameters such as hunger, appetite, satisfaction derived from food, fullness, and overall food quality. No significant differences were observed between the groups in terms of appetite, hunger, energy levels, or overall food quality, indicating that eating behavior and desire for food were generally maintained in both groups Table 6. However, a significant time-dependent effect was observed in food satisfaction in both the Forcslim and placebo groups, suggesting a reduction in enjoyment derived from food over the course of the study. Additionally, a significant decrease in feelings of fullness was noted in the Forcslim group from Week 0 to Week 12. Although appetite and hunger were not significantly influenced by supplementation, the reduced satisfaction from food in the Forcslim group may have contributed to a lower overall food intake.

Table 6.

Appetite markers for the Forcslim and Placebo groups.

Variable	Group	Week 0 (T1)	Week 4 (T2)	Week 8 (T3)	Week 12 (T4)	Significance
Appetite	Forcslim Placebo	4.6 ± 0.1 4.9 ± 0.6	4.9 ± 1.2 4.4 ± 1.4	4.6 ± 1.2 4.5 ± 1.5	4.4 ± 0.3 5.0 ± 1.2	Group Time Group × Time	0.930 0.870 0.680
Satisfaction from food	Forcslim Placebo	5.4 ± 1.3 5.8 ± 1.1	5.2 ± 0.4 5.8 ± 1.1	4.5 ± 1.1 5.6 ± 1.8	4.5 ± 1.7 5.2 ± 1.5	Group Time Group × Time	0.168 0.036 0.262
Hunger	Forcslim Placebo	4.3 ± 1.3 5.1 ± 1.2	3.7 ± 1.2 3.9 ± 1.3	4.3 ± 1.6 4.4 ± 1.2	3.3 ± 1.5 5.5 ± 1.0	Group Time Group × Time	0.052 0.635 0.155
Amount of energy	Forcslim Placebo	5.8 ± 2.2 5.5 ± 1.3	5.5 ± 1.1 7.0 ± 1.2	5.7 ± 2.2 5.9 ± 1.2	5.5 ± 1.6 5.8 ± 1.5	Group Time Group × Time	0.615 0.791 0.790
Feeling of fullness	Forcslim Placebo	5.5 ± 1.4 6.0 ± 1.2	4.6 ± 0.5 5.8 ± 1.4	5.3 ± 2.4 6.5 ± 1.4	4.3 ± 1.2 6.6 ± 1.6	Group Time Group × Time	0.050 0.070 0.052
Overall quality of food	Forcslim Placebo	4.5 ± 1.3 5.1 ± 1.2	5.3 ± 1.6 5.9 ± 1.2	4.7 ± 1.1 5.8 ± 1.3	4.2 ± 1.5 5.8 ± 1.2	Group Time Group × Time	0.112 0.462 0.142

4. Discussion

In the recent days, most of the prevailing diseases and nutritional disorders are treated with natural medicines. C. forskohlii is one of the predominant indigenous medicinal herbs in India, and it has been used as a traditional medicine healing different disorders [22]. The plant rootstock is utilized in Ayurveda and other medicine systems for treating various ailments, such as heart and lung conditions, asthma, digestive disorders, insomnia, muscle spasms, convulsions, and skin diseases [23]. C. forskohlii emerged as a taxon of significance in contemporary medicine because of the therapeutic properties of its phytoconstituents, especially forskolin, the primary diterpene component of this plant [24]. As the major chemical constituent of tubers, herbal formulations of forskolin act via multiple pharmacologic mechanisms. Forskolin activates adenylate cyclase enzymes, and among the nine types of adenylate cyclase in humans, forskolin can activate all, except type IX, which is found in spermatozoa [25]. Adenylate cyclase helps to increase the cyclic AMP level and eventually drives lipolysis or the breakdown of fat in adipose tissues [26]. The fatty acids subsequently released from adipose tissue depot also cause thermogenesis and an increase in lean tissue. Overall, forskolin may have the potential to reduce fat without reducing muscle mass [20]. Many investigations into the diverse pharmacological effects of C. forskohlii have been carried out, mainly in vitro and in vivo, but a few has been carried out in humans. Research has also been performed on the topical application of ointment containing forskolin to reduce regional fat from the thighs of obese women without diet or exercise. Significantly greater girth reduction was observed in the treated thigh in all trials [27]. Forskolin was developed into a gastro retentive floating drug delivery system that enhanced fat loss without loss of muscle mass and is available at conventional capsule dosages on the market [28]. It has been reported that, six overweight women were given 250 mg of standardized C. forskohlii extract containing 10% forskolin twice a day for eight weeks, resulting in an 8% body fat reduction and an average weight decrease [29]. The effects of C. forskohlii supplement on appetite were assessed in women who were mildly overweight, finding a significant reduction in the satisfaction of food consumed in the treated group, indicating less enjoyment in eating and consequently reduced food consumption intensity [21].

Our quasi-randomized, placebo-controlled, double-blind prospective clinical trial evaluated the efficacy and safety of C. forskohlii as a supplement for obese people. After 12 weeks of supplementation, we observed a significant time effect (p < 0.05) in weight, waist circumference, hip circumference, waist-to-hip ratio, total cholesterol, triglycerides, HDL, and heart rate between week 12 and baseline. Excess body fat around the waist and abnormal cholesterol or triglyceride levels are the key features of metabolic syndrome, as visceral fat triggers the secretion of adipocytokines such as leptin, interleukin-6, and adiponectin. Metabolic syndrome alters the secretion of these adipocytokines, contributing to the chronic inflammatory pathogenesis of the syndrome [30]. The waist circumference values observed in the study were 90.50 + 7.37 at baseline and 88.67 + 73.3 after 12 weeks. A reduction of 1.8 cm in waist circumference was observed in the experimental group after the study. Since waist circumference is a better marker of visceral fat, the significant reduction in waist circumference observed in our study is of potential clinical importance. In individuals with waist circumferences ranging from 60 to 135 cm, waist circumference changes between 1.8 cm and 4.1 cm are reported to be clinically significant [31]. The change in waist circumference could be achieved over a period of 12 months, but its clinical relevance is limited because of its uncertain long-term maintenance. Physical activity levels were monitored and stable throughout the study.

Dyslipidemia in obesity is generally characterized by high levels of triglyceride-rich lipoproteins and low levels of high-density lipoprotein cholesterol (HDL). Obesity causes a decrease in HDL [32] because of a marked shift from large cholesteryl ester-rich HDL to small and dense triglyceride-rich particles [33]. The serum lipid measurements in our study indicated that the triglyceride, cholesterol, and LDL-C values reduced from an average of 178.67–29.18, 194.80 + 31.57 and 95.57 ± 24.60 to 166.97 ± 29.66, 183.57 ± 31.39 and 94.03 + 21.61, respectively. The HDL-C value increased from an average of 35.23 ± 5.27 to 37.43 ± 4.63. Both the experimental and placebo groups presented comparatively low levels of plasma HDL-C at the baseline of the study. Following the 12-week intervention, the plasma concentration of HDL-C increased significantly in both groups. The circulating HDL-C shows an inverse relationship with dietary carbohydrate intake, as reported by Choi [34]. The significant rise in HDL-C concentration holds potential clinical importance as HDL-C has cardio-protective and anti-inflammatory properties due to its function in preventing LDL-C oxidization and therefore protects against atherosclerosis and coronary heart disease [35,36]. A reduction in the atherogenic index observed with Forcslim supplementation represents a favorable metabolic outcome. This decrease suggests an improvement in lipid profile balance and may indicate a potential reduction in the risk associated with cardiovascular disease (CVD) [37].

One of the purposes of this study was to investigate the safety effects of C. forskohlii supplementation on general health indicators. This was measured by monitoring heart rate and blood pressure changes during each visit and collecting serum and whole blood samples during week 0 and week 12 of the study, as previous research indicated that C. forskohlii causes an increase in heart rate and a decrease in blood pressure [38]. However, the findings of this analysis demonstrated that supplementation had no significant effect on either variable. The blood samples collected were assayed for liver enzymes, lipid profile, protein status, and fasting blood glucose. A significant time effect was observed for LDL, TOB, SGOT, and SGPT, whereas time effects were not observed for the other factors. A significant group effect was observed for total protein, and there was no significant group effect in all other parameters. These factors contribute to muscle, immune system, liver, and protein functions, respectively, in the body. Despite these changes, the values remained within normal ranges and were relatively small. Furthermore, no significant adverse events were reported during the study that could be attributed to the supplementation protocol. Therefore, C. forskohlii supplementation is not associated with any significant clinical side effects.

C. forskohlii has been described in both the Indian Pharmacopoeia and the Ayurvedic Pharmacopoeia of India without any toxic reports [39,40]. Very few significant risks with minor side effects have been reported so far. A study has evaluated the edible quality of the forskohli genotype, assessing its total sugar, starch, and protein content in fresh tubers and roots. Sarwar [41] suggested that C. forskohlii is safe for consumption and beneficial for medicinal purposes. Another study has been conducted to check the safety and efficacy of C. forskohlii extract, involving 29 healthy subjects, and tested over a 4-week period, increasing the dose from 250 to 1000 mg. According to the study, some of the subjects experienced mild gastrointestinal side effects, such as diarrhea and soft stool, after intake of C. forskohlii extract. Following the administration of each dose, 6–7 subjects reported very mild gastrointestinal adverse events. They also reported that the C. forskohlii formulation could be taken orally for up to 1000 mg per day [42]. According to Kapewangolo et al., Coleus was widely used in African countries as a home remedy and was much less cytotoxic [43]. C. forskohlii extract supplementation is well-tolerated and is generally recognized as safe for use [44].

There are a few limitations to our study that should be taken into account. The most significant limitation is the comparatively small sample size of 60 participants (30 patients and 30 healthy controls), which could restrict how broadly the results can be applied. The limited quasi-randomized size highlights the need for larger, more diverse populations and longitudinal follow-up to validate our results across more diverse populations and clinical settings. To further understand the mechanisms and long-term effects of C. forskohlii (Forcslim), longer follow-up periods in future research are advised. This study provides useful information that can help develop a more thorough and successful anti-obesity strategy.

5. Conclusion

In conclusion, the findings from this 12-week clinical study suggest that Forcslim may possess weight- and fat-reduction properties. Supplementation over the study period demonstrated a significant time-dependent effect on body weight, waist circumference, hip circumference, and waist-to-hop ratio in obese subjects compared to the placebo group. The 12-week treatment did not produce any subjective or objective side effects in either the active compound or the placebo-receiving group. Overall, these results indicate that Forcslim may serve as a potential anti-obesity supplement with a favorable safety profile.

Author contributions

Conceptualization: [Firoz Hirehal Hussain Mirza]; methodology: [Sadashiva Channangihalli Thimmegowda and Firoz Hirehal Hussain Mirza]; formal analysis and investigation: [Sadashiva Channangihalli Thimmegowda, Rajesh venkataraman and Ravi B Nagarajaiah]; writing – original draft preparation: [Firoz Hirehal Hussain Mirza]; writing – review and editing: [Sadashiva Channangihalli Thimmegowda, Rajesh venkataraman and Ravi B. Nagarajaiah].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

No funding.

Data availability statement

All relevant materials are presented in the present manuscript.

Ethics approval and consent to participate

The study protocol was approved by Institutional Ethics Committee of AH&RC, Adichunchanagiri Hospital. Written informed consent was obtained from all participants, and all experiments were conducted in accordance with relevant guidelines and regulations. The protocol is registered in ClinicalTrials.gov (ID: (IEC/AHRC/CT/004/2022).