The Effect of Green Coffee Extract on Blood Glucose Homeostasis in Healthy Adults

Green coffee extract (GCE) supplementation has been shown to induce favourable benefits on glucose metabolism and weight management. These effects are attributed to its high chlorogenic acid (CGA) content, recognized for its anti-inflammatory properties. Chronic CGA supplementation (4-12 weeks) has been linked to reduced body mass, waist circumference, fasting glucose, and insulin resistance in both healthy adults and those with metabolic disease. Yet, comparably fewer studies have examined the effects of acute GCE supplementation and yielded inconsistent results, likely owing to variations in study design and participant selection, which limit our understanding of its acute effects.

Alpha-lipoic acid (ALA) is a cofactor of mitochondrial dehydrogenase complexes and a potent antioxidant that has been implicated in glucose metabolism. ALA increases the translocation of glucose transporter type 4 to cell membranes and improves insulin sensitivity through adenosine monophosphate-activated protein kinase (AMPK) activation, both of which facilitate glucose uptake. Furthermore, 300mg of ALA has been shown to improve endothelial function and reduce fasted blood glucose concentrations in clinical populations. Therefore, investigating the effects of a lower ALA dosage, specifically 200mg, compared to 400mg in the acute fed state, as well as whether ALA and GCE can act synergistically to elicit favourable effects on postprandial glucose control requires further investigation in healthy adults.

Berberine, a known AMPK activator, is a natural alkaloid present in various parts (root, stem, fruit, bark) of multiple plants including, in particular, species found in the Coptis, Hydrastis, and Berberis genus. Chronic berberine supplementation (lasting 1 month) resulted in reduced fasting blood glucose, 2-hour postprandial blood glucose levels, and insulin resistance index scores, outperforming standard care alone in individuals with metabolic syndrome, suggesting that berberine may assist with blood glucose regulation in this population. Berberine has low bioavailability (<1%) reported in both animal and human models largely due to poor intestinal absorption and high levels of first-pass removal in the intestines and liver. To overcome this limitation, higher doses of berberine (500-1500mg) are commonly administered, which may lead to gastrointestinal adverse events. Dihydroberberine (DHB), a highly bioavailable form of berberine, has been shown to achieve greater area under the curve as well as peak berberine concentrations when compared to oral ingestion of 500 mg berberine or placebo in humans. However, whether acute DHB supplementation in combination with green coffee extract elicits beneficial effects on postprandial glucose handling in healthy adults has yet to be elucidated.

The purpose of the current study is to determine the impact of acute supplementation of GCE on postprandial glycemia in healthy adults. A secondary objective is to evaluate the effect of GCE on postprandial insulinemia, insulin sensitivity, glucose oxidation and appetite perceptions. The investigators hypothesize that compared to placebo, a 200mg dose of GCE combined with 400 mg alpha-lipoic acid consumed 30 min prior to a 75g oral glucose challenge will 1) lower 2-hour glucose incremental area under the curve (AUC; primary outcome); 2) lower 2-hour insulin incremental AUC and insulin resistance (Matsuda Index); 3) increase rates of glucose oxidation; and 4) lower appetite perceptions. The investigators also hypothesize that the 200 mg dose of GCE combined with 400 mg alpha-lipoic acid will exert effects like, or greater than, the 200 mg dose of GCE with 200 mg of DHB.

Inclusion criteria

• Males and females 18-45 years
• BMI between 18.5-30 kg/m2
• No history of smoking or cardiovascular and metabolic diseases (stroke, hypertension, type II diabetes) or other diseases that could impact the study outcomes
• Weight stable (within ±2kg for 6 months)
• Generally healthy as assessed by medical and physical activity questionnaires
• No oral contraceptive use except for triphasic contraceptives

Exclusion criteria

• Any concurrent medical, psychiatric, or orthopedic condition that, subject to investigators' discernment, would negatively affect the subject's ability to comply with the study requirements
• Any history of cardiovascular, neurological, respiratory, skeletal muscle or metabolic disease
• Using medication to manage blood glucose or lipid metabolism
• Bleeding disorders or antiplatelet/ anticoagulation therapy
• Currently using (or use within the last 3 months) monophasic or biphasic oral contraceptives
• Currently supplementing with GCE, ALA, or dihydroberberine
• Any known allergies to green coffee extract, alpha-lipoic acid, dihydroberberine or berberine, or supplementing within the last 3 months
• Currently pregnant or lactating
• Have irregular menstrual cycles (<21 days or >35 days)
• Any form of cancer currently or in the last 5 years
• Are recreational smokers of any form (tobacco or cannabis)
• Use of corticosteroids, testosterone replacement therapy, or any anabolic steroid
• Not willing to consume the 24-hour control diet prior to metabolic trials
• Any current Illness which could interfere with the study (e.g., prolonged diarrhea, regurgitation, etc.)