Mg Of Epigallocatechin Gallate Research Articles

The Effects of Epigallocatechin-3-Gallate Nutritional Supplementation in the Management of Multiple Sclerosis: A Systematic Review of Clinical Trials.

Multiple sclerosis (MS) is a chronic, debilitating neurological condition for which current treatments often focus on managing symptoms without curing the underlying disease. Recent studies have suggested that dietary supplements could potentially modify disease progression and enhance quality of life. This systematic review aims to evaluate the efficacy and safety of epigallocatechin-3-gallate (EGCG) as a dietary supplement in patients with MS, with a specific focus on its impact on disease progression, symptom management, and overall quality of life. We conducted a comprehensive systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing an exhaustive search across the databases PubMed, Scopus, and Web of Science up to 23 February 2024. Eligible studies were randomized controlled trials. Nine clinical trials involving 318 participants were analyzed, with dosages ranging from 600 mg to 1200 mg of EGCG daily, although most studies had only a 4-month follow-up period. Results indicated that EGCG supplementation, particularly when combined with coconut oil, led to significant improvements in metabolic health markers and functional abilities such as gait speed and balance. One trial observed significant improvements in the Berg balance scale score from an average of 49 to 52 after four months of treatment with 800 mg of EGCG daily. Additionally, interleukin-6 levels significantly decreased, suggesting anti-inflammatory effects. Measures of quality of life such as the Beck Depression Inventory (BDI) scale showed significant improvements after EGCG supplementation. However, primary outcomes like disease progression measured by the Expanded Disability Status Scale (EDSS) and Magnetic Resonance Imaging (MRI) of lesion activities showed minimal or no significant changes across most studies. EGCG supplementation appears to provide certain symptomatic and functional benefits in MS patients, particularly in terms of metabolic health and physical functionality. However, it does not significantly impact the primary disease progression markers such as EDSS scores and MRI lesions. These findings underscore the potential of EGCG as a supportive treatment in MS management, though its role in altering disease progression remains unclear. Future research should focus on long-term effects and optimal dosing to further elucidate its therapeutic potential.

EGCG’s effects on Mean Arterial Pressure and Heart Rate Variability and Their Correlations with Metabolic and Hormonal Profiles in Obese Subjects

This study aimed to investigate the effects of epigallocatechin gallate (EGCG), a potent polyphenol found in green tea, on mean arterial pressure (MAP) and heart rate variability (HRV) in obese subjects along with their associations with metabolic factors. We hypothesized that EGCG treatment could significantly reduce MAP and sympathetic tone, represented by decreased low-frequency power (LF) and LF-to-high frequency power (HF) ratio. Furthermore, we expected that systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP would be positively correlated with obesity parameters, LF, and LF-to-HF ratio. This study is a double-blind, randomized controlled trial. Thai obese subjects with a body mass index (BMI) ≥ 25 kg/m2 (criteria for an Asian population) were randomly allocated into EGCG and placebo groups and received a capsule of 150 mg of EGCG or starch, respectively, twice a day without any dietary restrictions. Clinical and anthropometric data, as well as spontaneous 5-minute HRV measurements in both time and frequency domains, were assessed at baseline (week 0), week 4, and week 8. Additionally, 8-hour fasting blood samples were collected at weeks 0 and 8 to measure metabolic and hormonal levels. EGCG treatment for 8 weeks significantly reduced MAP compared to week 0 and week 4 (P < 0.05 for all). In the EGCG treatment group, there was a significant increase in the LF-to-HF ratio and a nonsignificant decrease in HF at week 8 compared to week 0. LF showed a trend toward increasing in week 8 of EGCG treatment compared to week 4. For correlation analysis at week 0, SBP had significant positive correlations with BMI, percent fat, fat mass, serum leptin and insulin levels, and the homeostatic model assessment for insulin resistance (HOMA-IR) (R = 0.468-0.593, p<0.05 for all) but had negative correlations with the quantitative insulin sensitivity check index (QUICKI) and HDL-cholesterol (R = (-0.437)-(-0.468), P <0.05 for all). DBP was positively correlated with age and HF in normal units (nu) (R = 0.412-0.568, p<0.05 for all), but was negatively correlated with height, HDL-cholesterol, LF in ms (R = (-0.379)-(-0.509), P <0.05 for all). MAP showed significant positive correlations with age, BMI, percent fat, fat mass, serum leptin levels, and HOMA-IR (R = 0.370-0.459, P < 0.05 for all), but had a negative correlation with HDL-cholesterol (R = -0.522, P = 0.004). EGCG treatment over an 8-week duration reduced MAP, a pivotal component of overall blood pressure in obese individuals, and exhibited a significant increase in the LF/HF ratio, tending toward an increase in LF and a non-significant decrease in HF. We postulate that the decrease in MAP may be attributed to EGCG's direct or indirect vasodilatory effects, potentially through the stimulation of nitric oxide production, reduced oxidative stress, and/or decreased levels of kisspeptin, a vasoconstrictive substance, as reported by previous studies. An increase in the LF/HF ratio could reflect a shift toward sympathetic nervous system dominance (LF) and/or a decrease in parasympathetic nervous system activity (HF) indicating a compensatory response to the reduced blood pressure post-vasodilation. HDL cholesterol showed negative correlations with SBP, DBP, and MAP, reflecting its protective benefit against high blood pressure. In summary, 8 weeks of EGCG treatment resulted in a significant decrease in MAP and an increase in the LF/HF ratio, reflecting EGCG’s primary vasodilatory effects and a compensatory increase in sympathetic nervous system activity. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lipid Profile in Multiple Sclerosis: Functional Capacity and Therapeutic Potential of Its Regulation after Intervention with Epigallocatechin Gallate and Coconut Oil.

Multiple sclerosis (MS) patients present dyslipidemia and functional disability. Epigallocatechin gallate (EGCG) and coconut oil have been shown to be effective against dyslipidemia. To analyze the relationship between lipid profiles, fat consumption, and functional disability in patients with MS after administering EGCG and coconut oil. A four-month pilot study was conducted on 45 MS patients, divided into an intervention group (IG) and a control group (CG). The IG received 800 mg of EGCG and 60 mL of coconut oil. Lipid profiles were measured before and after the intervention, along with other data such as dietary habits, inflammatory markers, and functional capacity. Dyslipidemia did not correlate with the patients' fat consumption. After the intervention, triglycerides (TG) levels were lower in IG compared to CG. This decrease was positively correlated with an improvement in functional disability (determined by the Expanded Disability Status Scale (EDSS)) and negatively with high-density cholesterol (HDL) and apolipoprotein A1. Significant and positive correlations were observed between EDSS and C-reactive protein (CRP) in the IG. These changes in the IG could be related to body fat decrease, whose percentage shows a positive correlation with CRP and TG levels, and a negative correlation with HDL levels. Patients with MS present a certain type of dyslipemia not associated with their nutritional habits. The administration of EGCG and coconut oil seems to decrease blood TG levels, which could explain the functional improvements.

Green tea extract supplementation does not modify plasma concentration of F2-isoprostanes in women who are postmenopause: Findings from a randomized controlled trial

Green tea extract (GTE) is a potential mitigator of oxidative stress, and F2-isoprostanes are a reliable biomarker of oxidative stress. Genetic polymorphisms in the catechol-o-methyltransferase (COMT) gene may modify tea catechin metabolism, prolonging exposure. We hypothesized that GTE supplementation would decrease plasma F2-isoprostanes concentrations compared with placebo and that participants with the COMT genotype polymorphisms would experience a more significant expression of this outcome. This study was a secondary analysis of the Minnesota Green Tea Trial, a randomized placebo-controlled, double-blinded trial investigating the effects of GTE in women who were generally healthy and postmenopausal. The treatment group consumed 843 mg of epigallocatechin gallate daily for 12 months versus placebo. Participants in this study had a mean age of 60 years, were predominantly White, and most had a healthy body mass index. GTE supplementation did not significantly change plasma F2-isoprostanes concentrations compared with placebo after 12 months (P for overall treatment = .07). There were no significant interactions between treatment and age, or body mass index, physical activity, smoking history, and alcohol intake. COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentrations in the treatment group (P = .85). Among participants in the Minnesota Green Tea Trial, consuming GTE supplements daily for 1 year did not result in a significant decrease in plasma F2-isoprostanes concentrations. Likewise, the COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentrations.

Effect of Green Tea Extract Supplementation and Impact of Catechol-O-Methyltransferase Genotype on Plasma Concentration of F2-Isoprostanes in Women Who Are Post-menopause

ObjectivesGreen tea extract (GTE) is a potential mitigator of oxidative stress. F2-isoprostanes are a reliable and easily measured marker of oxidative stress. Genetic polymorphisms in the catechol-o-methyltransferase (COMT) gene may modify green tea catechin metabolism and potentially prolong exposure to catechins in those with lower activity COMT genotypes. The objective of this study was to assess if GTE supplementation would result in a decrease in plasma F2-isoprostanes concentration as compared to placebo. A secondary objective was to determine the impact of the COMT genotype on F2-isoprostanes concentration among participants receiving GTE. MethodsThis study is a secondary analysis of the Minnesota Green Tea Trial (MGTT), a randomized placebo-controlled, double-blinded trial investigating the effects of GTE in nearly 1000 women who were generally healthy and post-menopause. The treatment group consumed 843 mg of epigallocatechin gallate daily for 12 months as two capsules twice daily, vs identically appearing placebo capsules for controls. The current analysis was conducted using data from the 254 participants who had plasma F2-isoprostanes analyzed by a validated gas chromatography-mass spectrometry method. ResultsThe mean values of age and BMI were 59.7 years and 25.1 kg/m2, respectively, and more than 96% of the women were non-Hispanic white. Using ANCOVA model adjusting for dietary protein intake there was no statistically significant difference in plasma F2-isoprostanes concentrations between participants in the GTE (n = 133) as compared with the placebo group (n = 125) after 12 months (P = 0.557). There were no significant interactions between treatment and age, or BMI, physical activity, smoking history and alcohol intake. Additionally, COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentration in those who consumed GTE supplement (P = 0.603). ConclusionsAmong participants in the MGTT who were 50–70 years old and post-menopause, consuming GTE supplements daily for one year did not result in a significant decrease in plasma F2-isoprostanes concentration, a biomarker of oxidative stress. Likewise, COMT genotype did not modify the effect of GTE supplementation on F2-isoprostanes concentration. Funding SourcesNIH/NCI (Grant R01 CA127236).

Green Tea Extract to Prevent Colorectal Adenomas, Results of a Randomized, Placebo-Controlled Clinical Trial.

Preclinical, epidemiological, and small clinical studies suggest that green tea extract (GTE) and its major active component epigallocatechingallate (EGCG) exhibit antineoplastic effects in the colorectum. A randomized, double-blind trial of GTE standardized to 150 mg of EGCG b.i.d. vs placebo over 3 years was conducted to prevent colorectal adenomas (n = 1,001 with colon adenomas enrolled, 40 German centers). Randomization (1:1, n = 879) was performed after a 4-week run-in with GTE for safety assessment. The primary end point was the presence of adenoma/colorectal cancer at the follow-up colonoscopy 3 years after randomization. The safety profile of GTE was favorable with no major differences in adverse events between the 2 well-balanced groups. Adenoma rate in the modified intention-to-treat set (all randomized participants [intention-to-treat population] and a follow-up colonoscopy 26-44 months after randomization; n = 632) was 55.7% in the placebo and 51.1% in the GTE groups. This 4.6% difference was not statistically significant (adjusted relative risk 0.905; P = 0.1613). The respective figures for the per-protocol population were 54.3% (151/278) in the placebo group and 48.3% (129/267) in the GTE group, indicating a slightly lower adenoma rate in the GTE group, which was not significant (adjusted relative risk 0.883; P = 0.1169). GTE was well tolerated, but there was no statistically significant difference in the adenoma rate between the GTE and the placebo groups in the whole study population.

Possible Role of Butyrylcholinesterase in Fat Loss and Decreases in Inflammatory Levels in Patients with Multiple Sclerosis after Treatment with Epigallocatechin Gallate and Coconut Oil: A Pilot Study

(1) Background. Multiple sclerosis (MS) is characterised by the loss of muscle throughout the course of the disease, which in many cases is accompanied by obesity and related to inflammation. Nonetheless, consuming epigallocatechin gallate (EGCG) and ketone bodies (especially β-hydroxybutyrate (βHB)) produced after metabolising coconut oil, have exhibited anti-inflammatory effects and a decrease in body fat. In addition, butyrylcholinesterase (BuChE), seems to be related to the pathogenesis of the disease associated with inflammation, and serum concentrations have been related to lipid metabolism. Objective. The aim of the study was to determine the role of BuChE in the changes caused after treatment with EGCG and ketone bodies on the levels of body fat and inflammation state in MS patients. (2) Methods. A pilot study was conducted for 4 months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Fat percentage and concentrations of the butyrylcholinesterase enzyme (BuChE), paraoxonase 1 (PON1) activity, triglycerides, interleukin 6 (IL-6), albumin and βHB in serum were measured. (3) Results. The intervention group exhibited significant decreases in IL-6 and fat percentage and significant increases in BuChE, βHB, PON1, albumin and functional capacity (determined by the Expanded Disability Status Scale (EDSS)). On the other hand, the control group only exhibited a decrease in IL-6. After the intervention, BuChE was positively correlated with the activity of PON1, fat percentage and triglycerides in the intervention group, whereas these correlations were not observed in the control group (4). Conclusions. BuChE seems to have an important role in lipolytic activity and the inflammation state in MS patients, evidenced after administering EGCG and coconut oil as a βHB source.

The Impact of Epigallocatechin Gallate and Coconut Oil Treatment on Cortisol Activity and Depression in Multiple Sclerosis Patients.

(1) Background: Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), whose main source is coconut oil, have shown emotional benefits and body fat loss. The aim of this study was to assess the impact of EGCG and coconut oil on cortisol activity related to fat loss and depression in MS patients. (2) Methods: The study involved 51 MS patients who were randomly divided into an intervention group or a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, which were included in their daily diet for four months. The control group received placebo and all patients followed an isocaloric diet. A blood sample was collected before and after the four-month period, and levels of cortisol, albumin and BHB were measured in serum. In addition, immediately before and after the intervention, anthropometric variables were measured: waist-to-hip ratio (WHR), body fat mass percentage, fat weight, total weight, and muscle mass percentage. Depression was assessed with the Beck Depression Inventory II (BDI-II). (3) Results: No significant changes were obtained in cortisol levels in any of the groups, and there was a significant increase in albumin in the blood of the intervention group only that could lead to a decrease in serum free cortisol. In addition, it was observed a significant decrease in levels of depression and abdominal fat. (4) Conclusions: EGCG combined with coconut oil increase the concentration of albumin in blood and produce less depression in MS patients.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time–condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.

Effects of Green Tea on Various Types of Indolent Low Grade B-Cell Lymphomas

Low grade B cell neoplasms, such as chronic lymphocytic leukemia (CLL), usually are asymptomatic when diagnosed and undergo close observation. Many patients with low grade B cell lymphomas and leukemias (LGBCL) appreciate reassurance that not treating at time of diagnosis is the appropriate management. Society has long focused on diet and lifestyle changes as an alternative to medication; however, there is limited data to which these changes can assist with hematologic disorders. Green tea (GT) has been studied in regard to its effects on longevity and health. A cohort study followed 52,000 adults over 13 years and found that the frequency of GT consumption was inversely associated with risk of total hematologic neoplasms (Takada M, et al., 2019). There are several other studies that report key oncologic pathways are disrupted by a compound found in GT called epigallocatechin-gallate (EGCG) (Farooqi A, et al., 2020). Following a case series publication by Dr. Shanafelt, the National Cancer Institute sponsored clinical trials through the Mayo Clinic, evaluating EGCG in 42 patients with asymptomatic CLL. Patients received 2000mg EGCG twice daily for 6 months. Results showed 69% of patients had a biological response with greater than 20% reduction in absolute leukocyte count (ALC) and/or greater than 30% in reduction in size of the lymph node area utilizing standard assessment criteria (Shanafelt T. et al. 2013). This data encouraged our practice to recommend to patients to drink two bags of GT in steamy hot water daily. We studied 11 patients with indolent CLL, follicular lymphoma (FL), Waldenstrom macroglobulinemia (WM), monoclonal gammopathy of undetermined significance (MGUS), and splenic Marginal zone lymphoma (MZL). No patient was symptomatic. Disease makers were recorded over time during their routine visits for observation. The markers used were ALC for CLL and MZL, standardized uptake value (SUV) on PET scan for lymph node detection for FL, immunoglobulin level as well as monoclonal protein (M-protein) measured by SPEP for MGUS, and IgM and M-protein for WM. One patient with extensive cutaneous plaque psoriasis had routine skin checks. The results were recorded in the electronic health record over varying time periods based on patient presentation and follow up. Six patients with CLL responded to GT, with reductions in ALC. In patient 1, ALC decreased by 37% over 48 months. Patient 2's ALC decreased by 68% over 102 months. Patient 3's ALC decreased by 74% in 96 months. Patient 4 had a drastic increase in ALC from 23,900 to 72,400 over three years before GT. Once starting GT, his ALC plateaued at 72,000 and has remained stable for 65 months. Patient 5 had decrease ALC of 66% over 99 months. Patient 6 with WM had a 79% decrease in IgM over 65 months drinking GT. M-protein decreased by 81%. Patient 7 had a decrease in IgM by 26% and a 24% decrease in M-protein over 36 months. Patient 8 with MGUS had a decrease in IgG by 25% over 77 months. Patient 9 had a decrease in IgG by 23% with M-protein reduction of 43%. Due to compliance issues, duration of therapy was unknown. Patient 10 with ZL had an ALC reduction of 73% over 95 months. Lastly, patient 11 with FL and psoriasis was treated with GT for 23 months. There was a reduction of external iliac and inguinal lymph node SUV by 38% and 83% over 23 months, respectively. It was also noted of a significant improvement of extensive plaque psoriasis during this time on GT (Table 1). The 11 patients highlighted in the practice had improvement in biomarkers and lymphadenopathy during the time they took daily GT. The EGCG study at Mayo Clinic, in which CLL patients took up to 4,000mg of EGCG per day, had significant responses as well as adverse effects including transaminitis. This compares to the population in our study, which includes various types of LGBCL and MGUS that were taking at most 200mg of EGCG per day and had significant responses with no adverse effects. The use of low dose EGCG for inducing clinical improvement of these types of LGBCL and MGUS may be used to delay the onset of starting therapy, thus forestalling immunosuppressive treatment and associated toxicities. Larger randomized control trials involving other forms of indolent LGBCL and MGUS would be significant for the potential of GT being a safe, non-toxic lifestyle change that could benefit patients who do not require aggressive medical therapy for their neoplastic processes. Disclosures No relevant conflicts of interest to declare.

Effects of epigallocatechin gallate on total antioxidant capacity, biomarkers of systemic low-grade inflammation and metabolic risk factors in patients with type 2 diabetes mellitus: the role of FTO-rs9939609 polymorphism.

IntroductionType 2 diabetes mellitus (T2DM) is known as one of the most common metabolic diseases and FTO polymorphism has been implicated in the susceptibility to this disease. Epigallocatechin-3-gallate (EGCG) has shown favorable effects on risk factors related to T2DM. The present study aimed to investigate the effects of EGCG on total antioxidant capacity, biomarkers of systemic low-grade inflammation and metabolic risk factors in patients with T2DM considering the role of FTO polymorphism.Material and methodsIn this double-blind randomized clinical trial, 60 patients with T2DM (20–60 years) were randomly allocated to three groups. Group 1 received 300 mg of EGCG (TT genotype). Group 2 received 300 mg of EGCG (AA + AT genotypes) and Group 3 received placebo. We genotyped FTO (rs9939609) and measured body mass index (BMI), blood pressure, profile lipid, interleukin-6, high sensitivity C-reactive protein and total antioxidant capacity, before and after the intervention, at 2 months.ResultsIn carriers of A allele, EGCG intervention caused a significant decrease in BMI, diastolic blood pressure (DBP), mean arterial pressure and serum cholesterol level compared with placebo (p < 0.05). Also, we found a significant gene-treatment interaction effect between FTO-rs9939609 and EGCG on BMI and DBP (P > 0.05).ConclusionsThese findings suggest that carriers of the risk alleles (A) of FTO-rs9939609 have a better response to EGCG in improving BMI and DBP in patients with T2DM.

A Simple, Label-Free, and High-Throughput Method to Evaluate the Epigallocatechin-3-Gallate Impact in Plasma Molecular Profile.

Epigallocatechin-3-gallate (EGCG), the major catechin present in green tea, presents diverse appealing biological activities, such as antioxidative, anti-inflammatory, antimicrobial, and antiviral activities, among others. The present work evaluated the impact in the molecular profile of human plasma from daily consumption of 225 mg of EGCG for 90 days. Plasma from peripheral blood was collected from 30 healthy human volunteers and analyzed by high-throughput Fourier transform infrared spectroscopy. To capture the biochemical information while minimizing the interference of physical phenomena, several combinations of spectra pre-processing methods were evaluated by principal component analysis. The pre-processing method that led to the best class separation, that is, between the plasma spectral data collected at the beginning and after the 90 days, was a combination of atmospheric correction with a second derivative spectra. A hierarchical cluster analysis of second derivative spectra also highlighted the fact that plasma acquired before EGCG consumption presented a distinct molecular profile after the 90 days of EGCG consumption. It was also possible by partial least squares regression discriminant analysis to correctly predict all unlabeled plasma samples (not used for model construction) at both timeframes. We observed that the similarity in composition among the plasma samples was higher in samples collected after EGCG consumption when compared with the samples taken prior to EGCG consumption. Diverse negative peaks of the normalized second derivative spectra, associated with lipid and protein regions, were significantly affected (p < 0.001) by EGCG consumption, according to the impact of EGCG consumption on the patients’ blood, low density and high density lipoproteins ratio. In conclusion, a single bolus dose of 225 mg of EGCG, ingested throughout a period of 90 days, drastically affected plasma molecular composition in all participants, which raises awareness regarding prolonged human exposure to EGCG. Because the analysis was conducted in a high-throughput, label-free, and economic analysis, it could be applied to high-dimension molecular epidemiological studies to further promote the understanding of the effect of bio-compound consumption mode and frequency.

The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.

Background: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. Methods: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). Results: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. Conclusions: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

Acute Epigallocatechin 3 Gallate (EGCG) Supplementation Delays Gastric Emptying in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Background: Epigallocatechin 3 Gallate (EGCG) appears to act in appetite control through hormonal modulation. However, there is a lack of elucidation of EGCG’s action mechanisms, especially in humans. The aim of this study was to evaluate the effects of acute EGCG supplementation on gastric emptying and its relation to blood hormones, glucose and appetite perceptions in healthy women. Methods: 22 healthy adult women were included in a randomized, double-blind, placebo-controlled crossover study. On two separate occasions, 1 week apart from each other, we offered 800 mg of corn starch (placebo) or 752 mg of EGCG. Appetite was assessed through gastric emptying; perceptions of hunger, desire to eat and satiation; and plasma insulin, adiponectin, leptin and glucose concentrations. The evaluations were carried out in fasting, 30, 90 and 150 min after supplementation. Results: EGCG supplementation induced higher relative gastric volume at 30 and 90 min. Satiation at 90 min was higher in the EGCG group. Adiponectin concentrations at 150 min were higher with EGCG, but no difference was found for glucose, insulin and leptin concentrations. Conclusions: Acute EGCG supplementation is able to delay gastric emptying in healthy women to a small, but statistically significant extent. This study was registered at the Brazilian Registry of Clinical Trials (ReBEC) as RBR-9svwrv.

Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy volunteers.

The objective of this study is to assess the effects of green tea and its major catechin component, (-)-epigallocatechin gallate (EGCG), on CYP2C9-mediated substrate metabolism in vitro, and the pharmacokinetics of fluvastatin in healthy volunteers. The metabolism of diclofenac and fluvastatin in human recombinant CYP2C9 was investigated in the presence of EGCG. In a randomized three-phase crossover study, 11 healthy volunteers ingested a single 20-mg dose of fluvastatin with green tea extract (GTE), containing 150mg of EGCG, along with water (300mL), brewed green tea (300mL), or water (300mL) after overnight fasting. Plasma concentrations of fluvastatin and EGCG were measured by ultra-performance liquid chromatography with fluorescence detection and a single mass spectrometer. EGCG inhibited diclofenac 4'-hydroxylation and fluvastatin degradation with IC50 of 2.23 and 48.04μM, respectively. Brewed green tea used in the clinical study also dose-dependently inhibited the metabolism of diclofenac and fluvastatin in vitro. However, no significant effects of GTE and brewed green tea were observed in plasma concentrations of fluvastatin. The geometric mean ratios with 90% CI for area under the plasma concentration-time curve (AUC0-∞) of fluvastatin were 0.993 (0.963-1.024, vs. brewed green tea) and 0.977 (0.935-1.020, vs. GTE). Although in vitro studies indicated that EGCG and brewed green tea produce significant inhibitory effects on CYP2C9 activity, the concomitant administration of green tea and fluvastatin in healthy volunteers did not influence the pharmacokinetics of fluvastatin.

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects?

Introduction: epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea (Camellia sinensis) and has been associated with anti-obesity and anti-cancer effects, but the exact molecular mechanisms remain elusive. In this context, this study was designed to improve the understanding of the EGCG anti-obesity and anti-cancer action. Objectives: this study was designed to examine the effects of EGCG on the expression of genes involved in obesity and cancer pathways in the peripheral blood mononuclear cells of obese women. Material and methods: this longitudinal interventional study enrolled eleven women with severe obesity that were submitted to eight weeks of green tea (decaffeinated green tea capsules with 450.7 mg of EGCG, two capsules/day) supplementation (intervention group) and ten eutrophic women as a control group. Weight (kg), body mass index (BMI, kg/m2), fat mass (kg) and gene expression (qPCR method) were assessed before and after supplementation. HIF1-alpha (HIF1-α), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and rapamycin-insensitive companion of mTOR (RICTOR) were selected as potential targets. Results: after supplementation, body weight (114.9 ± 14.3 versus 115 ± 13.8 kg), body mass index (44.1 ± 3.7 versus 44.1 ± 3.9 kg/m2) and fat mass (47.6 ± 3.3 versus 47.3 ± 3.4 kg) did not change. EGCG upregulated the RICTOR and HIF1-α expression, however, did not modify PI3K expression. Conclusion: this study demonstrated that EGCG has a potential role to obesity and cancer related to obesity control and can be used not only for the purpose of weight loss, but also for the improvement of obesity-related comorbidities.

Dietary epigallocatechin 3-gallate supplement improves maternal and neonatal treatment outcome of gestational diabetes mellitus: a double-blind randomised controlled trial.

Gestational diabetes mellitus (GDM) is an increasing prevalent health risk in pregnant women. Epigallocatechin 3-gallate (EGCG) is known to benefit the insulin secretory machinery. We aimed to investigate the effect of daily dietary EGCG supplementation on both the maternal and neonatal treatment outcomes in GDM-affected pregnancies. In total, 472 pregnant women during their third trimester of pregnancy were diagnosed with GDM and subsequently enrolled into this trial. After exclusion, 404 patients were randomly assigned into EGCG and placebo study groups and subsequently administered either 500 mg of EGCG or placebo, respectively, on a daily basis until full term. The daily nutritional intake of all patients was monitored throughout the study. Maternal diabetic parameters at baseline and full term, including metabolism of glucose and insulin, as well as neonatal symptoms at birth, including birth weight, macrosomia, hypoglycaemia, respiratory distress and Apgar scores, were analysed. In total, 176 and 150 patients from the EGCG and placebo study groups, respectively, completed the trial. Patients from the EGCG group displayed significantly improved maternal diabetic parameters, and fewer cases of neonatal complications, compared to the placebo group. Daily dietary EGCG supplement improves both maternal and neonatal treatment outcomes of GDM.

Does supplementation with green tea extract improve acne in post-adolescent women? A randomized, double-blind, and placebo-controlled clinical trial

BackgroundGreen tea is believed to have beneficial effects in the prevention and treatment of acne. ObjectiveTo examine the effects of a decaffeinated green tea extract (GTE), providing a daily dose of 856mg of epigallocatechin gallate (EGCG) upon women with post-adolescent acne. MethodsA randomized, double-blind, placebo-controlled clinical trial was conducted from May 2012 through October 2013. A final group of 80 subjects were randomly assigned to receive either 1500mg of decaffeinated GTE or placebo (cellulose) daily for 4 weeks. Inflammatory lesion counts were used as the major outcome measurement. At baseline and after 4 weeks of treatment, anthropometric measurements, fasting glucose levels and a lipid profile were measured from both groups. ResultsSixty-four of 80 women, from 25 to 45 years of age with moderate-to-severe acne completed the study. Statistically significant differences were noted in inflammatory lesion counts distributed on the nose, periorally and on the chin between the two groups. However, there were no significant differences between groups for total lesion counts. Within-group comparison revealed that the GTE group had significant reductions in inflammatory lesions distributed on the forehead and cheek, and significant reductions in total lesion counts. GTE resulted in significant reductions in total cholesterol levels within the GTE group. ConclusionsGTE resulted in significant reductions in lesions located on the nose, perioral area and chin. More research is required to determine whether a decaffeinated GTE standardized for EGCG content will provide clinical benefits in women with post-adolescent acne.

Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies

ObjectivesPhase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects.Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. DesignPhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. ParticipantsRecruitment area (both studies): LSU MS Center, New Orleans, LA and general public from surrounding areas.Inclusion criteria (both studies): 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study.Exclusion criteria (both studies): 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. InterventionsPhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200mg of EGCG per capsule; total daily dose 800mg) for six months.PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. Outcome measuresPhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA.PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months.We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm×10cm×1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm3 voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing. ResultsPhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint.PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (G I, and 1G III). Median time to onset of abnormal LFTs was 20weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels.PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had similar levels of EGCG but differed in the levels of minor catechins. There were no significant differences between the lots on participants' median free EGCG plasma levels at either 3h or 8h as well as conjugated EGCG levels at 3h (all p>0.4, Wilcoxon exact test).Free EGCG levels at 8h correlated with changes in NAA adjusted by water content. A 1ng/ml higher EGCG plasma concentration correlated with a 0.9% increase in NAA[95% CI(0.5%,1.4%), visit*level interaction F=14.4, p<0.001]. However, EGCG plasma concentrations did not correlate with NAA adjusted by creatine (1ng/ml higher EGCG was associated with 0.02%,[95% CI(−0.27%,0.3%) change in NAA, p>0.5]). There was a trend towards an increase in creatine levels (referenced to water content) from baseline to exit (1 5% increase, [95% CI(−6%,17%), p=0.4]). The free EGCG levels at 8hours correlated significantly with change in creatine levels (1ng/ml higher EGCG level at 8h was associated with a 1.1% increase in creatine [95% CI(0.6%,1.6%)]). Thus it is possible that the discrepancy between the correlation of the EGCG 8h levels with NAA changes referenced to water and the 8h EGCG levels with NAA changes referenced to creatine was due to a change in creatine among the subjects with higher EGCG levels.Conjugated 3h and 8h levels and free 3h levels did not correlate with NAA changes (all p >0.5). Conclusions/classification of evidenceClass III evidence: Polyphenon E at a dose of 400mg of EGCG twice a day is not futile at increasing brain NAA levels. Class I evidence: some lots of Polyphenon E have a high risk of hepatotoxicity. FundingNational Center for Complementary and Alternative Medicine K23AT004433, National Multiple Sclerosis Society RG4816-A-1 and National Institute of General Medical Sciences 1 U54 GM104940. Mitsui Norin provided Polyphenon E and placebo and their representative reviewed the manuscript prior to publication. Mitsui Norin was not involved in other aspects of the study. The decision to submit the manuscript remained with the investigators. RegistrationNCT00836719 and NCT01451723NCT00836719NCT01451723.

Effects of rye bread enriched with green tea extract on weight maintenance and the characteristics of metabolic syndrome following weight loss: a pilot study.

We examined whether the incorporation of green tea extract enriched rye bread (GTRB) into the diet can improve weight loss (WL) maintenance and control of abnormalities linked to metabolic syndrome (MS). A total of 55 obese men and women (mean age: 53.0±7.0 years, body mass index: 35.0±5.5 kg m(-2)) were recruited. The study had a single-blind randomized study design and consisted of an 8-week WL phase with low-energy calorie diet, followed by a 12-week weight maintenance (WM) phase. During the WM phase, the subjects were randomized into two groups, receiving either the control rye bread (control group) or the GTRB (intervention group). The ingestion of 280 and 360 g GTRB provided daily totals of 123.2 and 158.4 mg caffeine, and 188.3 and 242.1 mg of epigallocatechin gallate, for women and men, respectively. After the WL phase, subjects lost 7.3±3.1 kg of their baseline body weight. GTRB intake did not significantly influence the maintenance of WL, high-density lipoprotein-cholesterol, triglycerides, and glucose concentrations. Although, it resulted in significant differences (mean difference [95% confidence interval]) between the treatment groups in the maintenance of waist circumference (-1.22 cm [-2.4, -0.02; P=.04]), the results were not clinically meaningful. Nevertheless, the ingestion of GTRB led to the maintenance of lower blood pressure (BP), also the proportion of subjects fulfilling the criteria of MS after the WM phase was lower in the intervention group than in the control group. Although GTRB consumption did not improve significantly the WL maintenance, it resulted in a better control of BP.