Reference
Zeng M, Hodges JK, Pokala A, et al. A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: a double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome. Nutr Res. 2024;124:94-110.
Study Objective
To evaluate the impact of decaffeinated green tea extract (GTE) on key cardiometabolic parameters, circulating endotoxin levels, inflammatory biomarkers, and intestinal permeability in healthy adults and those with metabolic syndrome (MetS)
Key Takeaway
In this small randomized, controlled trial (RCT), decaffeinated green tea extract was shown to reduce circulating endotoxins, support small-intestinal gut-barrier integrity, and improve glycemic control in both healthy adults and those with MetS without, interestingly, any impact on markers of systemic inflammation in either population.
Design
Randomized, double-blind, placebo-controlled, crossover trial
Participants
Investigators recruited 19 healthy adults and 21 adults with MetS from the Columbus, Ohio, area. Participants’ ages ranged from 18 to 65 years.
Investigators selected healthy participants according to the following criteria: body mass index (BMI) of 19 to 25 kg/m2; fasting glucose less than 100 mg/dL; fasting triglyceride less than150 mg/dL; fasting high-density lipoprotein cholesterol (HDL-C) greater than 50mg/dL (for women) or greater than 40 mg/dL (for men); and resting blood pressure less than 120/80 mm Hg.
Participants with MetS had at least 3 of the following risk factors: fasting blood glucose greater than 100 mg/dL; fasting triglyceride greater than 150 mg/dL; fasting HDL-C less than l50 mg/dL (for women) or greater than 40 mg/dL (for men); resting blood pressure greater than or equal to 130/85 mm Hg; and/or waist circumference greater than 89 cm (women) or 102 cm (men).
All participants were required to be nonsmokers and nonconsumers of tea and to maintain a low physical activity (less than 7 hours per week).
Intervention
Participants were randomly assigned to receive either a decaffeinated green tea extract confection or a placebo confection for a 4-week block, followed by a 4-week washout period; they then crossed over to the other treatment for a 4-week block.
The GTE confection was administered in 3 doses daily and provided a total daily dose of catechins equivalent to approximately 5 servings of green tea, or 890 mg of catechins. The GTE was sourced from Taiyo International, product Sunphenon 90LB.
The placebo confection contained the same ingredients as the GTE confection except with the GTE omitted and lime flavor added.
Participants received instructions on how to maintain a low-polyphenol diet, and investigators evaluated nutrition journals tracking days 0, 14, and 28.
Study Parameters Assessed
Investigators collected fasting blood work, 3-day nutrition journals, and anthropometric data on days 0, 14, and 28. They collected stool samples for 3 days prior to day 28 and urine samples on day 28 and the 24 hours following.
The study assessed the following parameters:
Intestinal Permeability
- Urinary excretion of lactulose/mannitol for small-intestine permeability and sucralose/erythritol for large-intestine permeability at 5 and 24 hours.
Intestinal Inflammation
- Fecal calprotectin
- Fecal myeloperoxidase
Cardiometabolic Parameters
- Fasting glucose
- Total cholesterol
- HDL
- Triglycerides
- Plasma insulin
- Homeostatic model assessment for insulin resistance (HOMA-IR)
- Aspartate transaminase (AST)
- Alanine transaminase (ALT)
- Ascorbic acid
- Uric acid
- BMI
- Waist circumference
- Blood pressure
Systemic Inflammation
- Tumor necrosis factor alpha (TNF-α)
- Interleukin 6 (IL-6)
Plasma Catechins and Metabolites
- Epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC)
- Gamma-valerolactone (γ-VL)
Endotoxemia
- Serum endotoxin (primary outcome)
- Ratio of lipopolysaccharide-binding protein to soluble cluster of differentiation 14
Primary Outcome
The impact of GTE on serum endotoxin levels in MetS subjects.
Key Findings
When compared to placebo:
GTE decreased serum endotoxin levels in both healthy (P<0.0001) and MetS participants (P=0.023).
In both cohorts, GTE decreased small-intestinal permeability for lactulose/mannitol at 5 hours (P=0.043) regardless of health status but without affecting large-intestinal permeability.
GTE decreased fecal concentrations of calprotectin and myeloperoxidase in the healthy and MetS cohorts, regardless of health status: calprotectin (Healthy, P=0.25; MetS, P=0.029); myeloperoxidase (Healthy, P=0.18; MetS, P=0.048).
GTE decreased glucose levels in both the healthy and MetS cohorts (Healthy, P=0.008; MetS, P=0.01).
GTE did not have a significant impact on systemic inflammatory markers TNF-α or IL-6.
Transparency
No conflicts were stated.
Practice Implications & Limitations
This small RCT further reinforces the benefits of consuming green tea and green tea extract for both the metabolic-syndrome and healthy cohorts, a finding corroborated by various observational and epidemiological studies examining cardiometabolic health.1
The trial found that in MetS participants, the equivalent of 5 cups of decaffeinated green tea (or 890 mg of catechin flavonoids) positively impacted gut-barrier function (particularly in the small intestine), improved intestinal inflammation (calprotectin and myeloperoxidase), and reduced levels of systemic endotoxins.
The study also demonstrated a glucose-lowering effect of GTE in both healthy and MetS participants over the 4-week period.
This may point to the general challenges in flavonoid absorption and poor bioavailability.
The study points to the beneficial impact of not only GTE but also polyphenol-rich compounds in general on intestinal inflammation and intestinal permeability, with the authors noting that the pleiotropic changes in cardiometabolic health we see with polyphenol-rich treatment programs can be explained, in part, by the significant impact these compounds are having in the intestinal environment.2
Interestingly, the study did not find positive changes in the systemic inflammatory biomarkers assessed (TNF-α and IL-6), despite reduction of systemic endotoxin levels in MetS participants. This may point to the general challenges in flavonoid absorption and poor bioavailability. Clinically it suggests the importance of having a comprehensive strategy when working with MetS patients that includes green tea and/or GTE.
Of note, investigators observed no impact on AST or ALT in either the healthy or MetS participants with the dosing strategy employed in the trial, further supporting the safety profile of green tea and GTE.
Overall, the findings support the use of green tea and GTE in clinical practice as a natural intervention to enhance gut health and improve glycemic control, particularly in individuals with metabolic syndrome.
Conflict of Interest Disclosure
The author declares no conflict of interest.
