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Research/Studies
The Highest Decrease in Body Fat Ever Observed in a Dietary Supplement*

 

Below is a sampling of research and studies that support the efficacy and power of OxySlender's active ingredient Metabolaid. Three additional studies on OxySlender's active ingredient, Metabolaid, were just completed  ("Effect of Hibiscus and Lippia Extract on Blood Pressure" "Efficacy of a Natural Ingredient on Blood Pressure," and "Effectiveness of a Natural Ingredient on Obesity,") and will be soon published. In addition to the studies cited below, the three recently completed studies show Metabolaid to very effacacious in reducing high blood pressure and in the significant reduction of body fat.

 

Metabolaid ® Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation. (Nutrients. 2018 Sep; 10(9): 1204. Published online 2018 Sep 1. doi: 10.3390/nu10091204)

 

Abstract

Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional medicine formulations to treat asthma and diabetes in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese medicine in the form of a tea to treat hypertension and inflammation. In the present study, we examined the synergistic effects of a formula of Metabolaid® (MetA), a combination of lemon verbena and hibiscus-flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced obese mice. The results showed that MetA decreased body weight, white adipose tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles, glucose levels, glucose tolerance, and cold-induced thermogenesis were significantly improved. Appetite-regulating hormones adiponectin and leptin were significantly increased and decreased, respectively, while the inflammatory-related factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated by MetA. Adipogenesis-activating gene expression was decreased, while increased thermogenesis-inducing genes were upregulated in the WAT, correlating with increased phosphorylation of AMPK and fatty-acid oxidation in the liver. ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165361/)

 

 

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity. (Nutrients  2017 Aug 20;9(8):907. doi: 10.3390/nu9080907)

 

Abstract

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. (https://pubmed.ncbi.nlm.nih.gov/28825642)

 

 

Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms. (Phytomedicine 2015 Jun 1;22(6):605-14.doi: 10.1016/j.phymed.2015.03.015. Epub 2015 Apr 10.)

 

Abstract

Background: There is growing evidence that natural products, mostly plant-derived polyphenols, are important in the relationship between nutrients and health in humans.

 

Purpose: We aimed to investigate if verbascoside (VB) and other lemon verbena polyphenols could ameliorate obesity-induced metabolic disturbances, as well as their putative mechanism.

 

Study Design: We used an insulin-resistant hypertrophic 3T3-L1-adipocyte model to test the effects of VB or lemon verbena extract on triglyceride accumulation, inflammation and oxidative stress and a murine model of diet-induced obesity to assess the in vivo metabolic response.

 

Results: Polyphenols decreased triglyceride accumulation, the generation of reactive oxygen species (ROS) and restored mitochondrial membrane potential in adipocytes. The underlying mechanisms seemed to occur via ROS-mediated downregulation of nuclear factor kappa-B transcription factor (NF-κB) and peroxisome proliferator-activated receptor gamma (PPAR-γ)-dependent transcriptional upregulation of adiponectin. We also observed a potent activation of AMP-activated protein kinase (AMPK), the mRNA expression upregulation of PPAR-α and the mRNA expression downregulation of fatty acid synthase. Experiments in mice suggested a significant improvement in fat metabolism.

 

Conclusion: Decreased lipogenesis, enhanced fatty acid oxidation and the activation of the energy sensor AMPK, probably through activating transcriptional factors, are involved in the observed beneficial effects. VB effects were less potent than those observed with the extract, so a potential synergistic, multi-targeted action is proposed. The polypharmacological effects of plant-derived polyphenols from lemon verbena may have the potential for clinical applications in obesity. (https://pubmed.ncbi.nlm.nih.gov/26055125)

 

A Randomized, Double-Blind, Placebo Controlled Trial to Determine the Effectiveness a Polyphenolic Extract ( Hibiscus sabdariffa and Lippia citriodora) in the Reduction of Body Fat Mass in Healthy Subjects(2020 Jan 6;9(1):55.doi: 10.3390/foods9010055)

 

Abstract

The location and quantity of body fat determine the health risks, limiting people with obesity. Recently, polyphenols have attracted the attention of the scientific community because of their potential use for the reduction of obesity. A proprietary formula comprised of a blend of Lippia citriodora and Hibiscus sabdariffa has been recognized for its high content of polyphenols, powerful antioxidant molecules that may prevent weight gain and could be helpful for the treatment of obesity, as proven previously by in vivo models. 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 subjects without a controlled diet. The intake of the extract for 84 days reduced body weight, the body mass index, and the fat mass measured with both bioimpedance and densitometry. This decrease in fat mass was observed to a greater extent, being significant, in the fat mass of the trunk (chest and torso).  (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022485)

 

 

Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial.  (DOI: 10.1039/C8FO00367J (Paper) Food Funct., 2018, 9, 3173-3184)

 

Abstract

Plant-derived polyphenols have shown potential to alleviate obesity-related pathologies by a multi-targeted mechanism in animal models and human intervention studies. A dietary supplement based on a combination of Lippia citriodora (LC) and Hibiscus sabdariffa (HS) polyphenolic extracts was assayed in a double blind and placebo-controlled intervention study with 54 overweight subjects.

 

Methods: Blood pressure, body weight, height, triceps, biceps and abdominal skinfold thickness, and arm and abdominal circumferences were taken at the baseline, 30 and 60 days of the intervention period. The validated Visual Analogue Scale used to record hunger and satiety-related sensations was passed at the beginning and at 15, 30, 45 and 60 days of the intervention. Subjective health status was assessed through the validated SF-36 questionnaire at the beginning and end of the study. Finally, plasma from fasting blood samples was obtained at the beginning, 30 and 60 days of the study.

 

Results: The results showed an improvement of anthropometric measurements, decreased blood pressure and heart rate and a more positive perception in the overall health status. We also observed that plant polyphenols increased anorexigenic hormones (glucagon-like peptide-1) and decreased orexigenic hormones (ghrelin).

 

Conclusions: Based on previous evidence we postulate that AMP-activated protein kinase may have a role in such effects through its capability to modulate energy homeostasis, total daily energy expenditure and lipid management. Although further research may be required, we propose that this polyphenolic combination may be used for weight management by increasing long-term weight loss maintenance through the modulation of appetite biomarkers. This may help to avoid the undesired weight regain typical of calorie restriction diets. (https://pubs.rsc.org/en/content/articlehtml/2018/fo/c8fo00367j)

 

 

Differential effects of a combination of Hibiscus sabdariffa and Lippia citriodora polyphenols in overweight/obese subjects: A randomized controlled trial (Sci Rep 2019 Feb 28;9(1):2999. doi: 10.1038/s41598-019-39159-5) (continued on next column).

Abstract

Plant-polyphenols have shown the capacity to ameliorate obesity-induced metabolic  disturbances, both in cell and animal models, where most therapeutic approaches have failed. On the basis of previous research, a dietary supplement containing 500 mg of a combination of polyphenolic extracts from Lippia citriodora L. and Hibiscus sabdariffa L. (LC-HS), in the context of an equilibrated isocaloric diet, was evaluated in a double blind, placebo-controlled and randomized trial in 56 obese/overweight subjects for two months. Compared to controls, the consumption of the LC-HS polyphenols showed significant improvements in body weight, abdominal circumference of overweight subjects (−6.79 ± 0.80 cm in overweight LC-HS group vs −1.85 ± 0.83 cm in controls, p < 0.001) and body fat % (−1.33 ± 0.15% in overweight LC-HS group vs −0.66 ± 0.17% in controls, p < 0.05). Heart rate and systolic blood pressure also presented significant improvements in overweight LC-HS participants. However, changes were more modest in obese subjects. Further, LC-HS extract significantly reduced lipid content and increased AMPK activity in a hypertrophied adipocyte cell model. Therefore, consumption of 500 mg/day of LC-HS extracts enriched in polyphenols for two months in the context of an isocaloric diet by overweight subjects decreased symptoms associated to obesity-related diseases. Modulation of fat metabolism in adipose tissue, probably mediated by AMPK activation, is proposed as a molecular target to be explored in future research. (https://pubmed.ncbi.nlm.nih.gov/30816148)

 

 

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity. (Nutrients  2017 (Aug 20;9(8):907. doi: 10.3390/nu9080907)

 

Abstract

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. (https://pubmed.ncbi.nlm.nih.gov/28825642)

 

 

High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a lemon verbena extract.  (Chromatogr A 2009 Jul 10;1216(28):5391-7. doi: 10.1016/j.chroma.2009.05.038. Epub 2009 May 21)

 

Abstract

High-performance liquid chromatography with diode array and electrospray ionization mass spectrometric detection was used to carry out the comprehensive characterization of a lemon verbena extract with demonstrated antioxidant and antiinflammatory activity. Two different MS techniques have been coupled to HPLC: on one hand, time-of-flight mass spectrometry, and on the other hand, tandem mass spectrometry on an ion-trap. The use of a small particle size C18 column (1.8 microm) provided a great resolution and made possible the separation of several isomers. The UV-visible spectrophotometry was used to delimit the class of phenolic compound and the accurate mass measurements on time-of-flight spectrometer enabled to identify the compounds present in the extract. Finally, the fragmentation pattern obtained in MS-MS experiments confirmed the proposed structures. This procedure was able to determine many well-known phenolic compounds present in lemon verbena such as verbascoside and its derivatives, diglucuronide derivatives of apigenin and luteolin, and eukovoside. Also gardoside, verbasoside, cistanoside F, theveside, campneoside I, chrysoeriol-7-diglucuronide, forsythoside A and acacetin-7-diglucuronide were found for the first time in lemon verbena.   (https://pubmed.ncbi.nlm.nih.gov/19500792)

 

 

A Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of a Combination of Lemon Verbena Extract and Fish Oil Omega-3 Fatty Acid on Joint Management (The Journal of Alternative and Complimentary Medicine Volume 17, Number 11, 2011, pp. 1051–1063)

 

Abstract

Objectives: The aim of this study was to test the efficacy of an antioxidant/anti-inflammatory supplement containing standardized lemon verbena (Aloysia triphylla, Lippia citriodora) extract and fish oil omega-3 fatty acid in a human pilot trial as an alternative treatment for joint management.

 

Methods and Design: First, antioxidant activity of the supplement was determined through an oxygen radical absorbance capacity (ORAC) assay. In a randomized, double-blinded placebo-controlled trial, 45 subjects with pain discomfort received the nutritional supplement or placebo for 9 weeks. Western Ontario MacMaster (WOMAC) and Lequesne’s questionnaires, which are disease-specific measurements validated to measure joint dysfunction and pain, were administered and evaluated once per week in the placebo and intervention groups.

 

Outcome Measures: Pain and stiffness symptoms, and joint function were determined once per week through recording their respective WOMAC and Lequesne’s scores in the placebo and intervention groups. Statistically significant differences were determined at every measurement point between the two groups.

 

Results: Lemon verbena extract showed strong antioxidant properties as measured by the ORAC assay. The nutritional supplement containing standardized lemon verbena extract (14% verbascoside, w/w) and fish oil omega-3 fatty acid reduced symptoms of pain and stiffness significantly, and improved physical function as shown by WOMAC and Lequesne’s scores after 9 weeks of treatment. WOMAC and Lequesne’s total scores decreased 53% and 78%, respectively, at the end of the study compared to initial conditions. Onset of the effect was observed at the third and fourth weeks, when statistically significant differences were detected, compared to

placebo.

 

Conclusions: This pilot study reveals that supplementation with lemon verbena combined with omega-3 fatty acids may be considered for further investigation as a complementary and alternative treatment for improving joint status in subjects with joint discomfort.  (https://pubmed.ncbi.nlm.nih.gov/22087615)

 

 

Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils’oxidative stress in chronic exercise. (Eur J Appl Physiol DOI 10.1007/s00421-010-1684-3)

 

Abstract

Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results.

 

The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase.

 

Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity.

 

Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation.

 

Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.  (https://pubmed.ncbi.nlm.nih.gov/20967458)

 

* The statement is deduced from Metabolaid research that concluded "The result of assessing body fat composition after 12 weeks taking Metabolaid® on healthy individuals resulted in a 6.9% decrease in body fat, one of the highest observed in dietary supplements! when compared to other botanical ingredients where clinical studies have been performed. Only those where double-blind, placebo-controlled studies were taken into account."

 

Some of the ingredients compared with Metabolaid (supplements and drugs):

 

Supplements:

1. Vs. other extracts (dietary supplement ingredients): (Sinetrol-Xpur 900 mg (Fytexia, Park SJ et al, J Medicinal Food 2020): 4.65% Body Fat loss in 12 weeks, assessed by DEXA Scan (Metabolaid is 6.9% body fat loss with 500 mg, Marhuenda J et al, 2020)

 

Garcinia Cambogia 1667-4668 mg (Various studies, see Haber S American Journal of Health-System Pharmacy for a Review): Mixed results, generally not significant vs. Placebo, numerous side effects

 

Drugs:

Vs. Semaglutide (type 2 diabetes/obesity drug, Nouck M et al, Diabetes Care 2016): Similar results in body weight loss as observed with Metabolaid, but only at the highest dosage (and with numerous side effects

 

 

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