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    The Hypoglycaemic Effects of the New Zealand Pine Bark Extract on Sucrose Uptake and Glycaemic Responses in Healthy Adults—A Single-Blind, Randomised, Placebo-Controlled, Crossover Trial
    (MDPI (Basel, Switzerland), 2025-07-09) Lim WXJ; Page RA; Gammon CS; Moughan PJ; Novoa DMA; Silva FRMB
    Background: The New Zealand pine bark has been demonstrated in vitro to inhibit digestive enzymes involved in carbohydrate digestion (alpha-amylase, alpha-glucosidase, and dipeptidyl-peptidase 4 (DPP-4)). Objective: This study aims to investigate the inhibitory effects of the New Zealand pine bark on sucrose uptake and glycaemic responses in humans. Methods: A single-blind, randomised, placebo-controlled, crossover trial was carried out involving healthy adults (n = 40 (M: 12, F: 28), 30.1 ± 1.3 years, BMI 23.4 ± 0.5 kg/m2, HbA1c 32.5 ± 0.6 mmol/mol, FBG 4.7 ± 0.1 mmol/L). A control (75 g of sucrose powder only), and two doses of the pine bark extract (50 and 400 mg) were provided on separate occasions, with 75 g of sucrose mixed in 250 mL of water. Blood samples were collected at −10, 0, 15, 30, 45, 60, 90, and 120 min via a finger prick test. A linear mixed model for repeated measures (SPSS v30, IBM) was applied, and data presented as model-adjusted mean ± SEM. Results: Compared to control (247.5 ± 14.0 mmol/L⋅min), the iAUCglucose was significantly reduced with the 400 mg dose (211.8 ± 13.9 mmol/L⋅min, 14.4% reduction, and p = 0.037), but not with 50 mg dose (220.8 ± 14.2 mmol/L⋅min, 10.8% reduction, and p = 0.184). Compared to control (9.1 ± 0.2 mmol/L), glucose peak value was significantly reduced with the 50 mg dose (8.6 ± 0.2 mmol/L, 5.5% reduction, and p = 0.016) but not with the 400 mg dose (8.7 ± 0.2 mmol/L, 4.4% reduction, and p = 0.093). There were no statistically significant changes in postprandial insulin levels with the pine bark extract compared to control. Conclusions: The New Zealand pine bark extract attenuated sucrose uptake with improved glycaemic responses, and may therefore be useful as a hypoglycaemic adjunct to the diet.
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    Hypoglycemic effects of antioxidant-rich plant extracts on postprandial glycemic responses in participants with prediabetes (GLARE study)
    (Food Science Publisher on behalf of the Academic Society for Functional Foods and Bioactive Compounds (ASFFBC), 15/11/2021) Lim WXJ; Gammon CS; Von Hurst PR; Chepulis L; Mugridge O; Page RA
    Background: Plant extracts may help to improve glycemic control in individuals with poor glycemic control. However, few studies have been investigated in the prediabetes cohort, which is a high-risk condition for T2DM. Thus, this study aimed to investigate the acute effect of grape seed, rooibos tea, and olive leaf extracts on postprandial blood glucose and insulin in participants with prediabetes. Methods: An acute, single-blind, placebo-controlled, non-randomized, crossover study (ACTRN12617000837325) where placebo and extracts of grape seed, rooibos tea and olive leaf standardized for total antioxidant capacity were given separately during an oral glucose tolerance test to participants (n=19, five men and fourteen women, aged 65.0 ± 1.6 years, Body Mass Index (BMI) 27.3 ± 1.1 kg/m2) with prediabetes (Glycated hemoglobin A1c (HbA1c) 42 ± 1 mmol/mol). The primary outcome incremental area under the curve of glucose (iAUCglucose) was examined with other glycemic measures. Data was analyzed using linear mixed model for repeated measures. Secondary analysis was conducted by stratifying participants into either a healthier or less healthy subgroup based on the postprandial time to glucose and insulin peaks, with the less healthy subgroup experiencing delayed glucose and/or insulin peaks. Results: There were no overall significant changes to glucose and insulin measures between all plant extracts and placebo (p>0.05). Upon secondary analysis, all extracts affected glycemic responses in the less healthy subgroup. Compared to placebo, grape seed reduced plasma iAUCglucose (p=0.016, 21.9% reduction), 2 h postprandial glucose (2hPG) (p=0.034, 14.7% reduction) and metabolic clearance rate of glucose (MCRglucose) (p=0.016, 16.7% increase). It also improved insulin indices such as 2 h postprandial insulin (2hPI) (p=0.029, 22.4% reduction) and Stumvoll overall insulin sensitivity index (ISIoverall) (p=0.028, 15.0% increase). Rooibos tea extract significantly improved β-cell function as demonstrated by the increased oral disposition index (DI) (p=0.031, 32.4% increase) compared to placebo. Olive leaf extract significantly increased incremental area under the curve of insulin (iAUCinsulin) (p=0.040, 16.7% increase). Conclusion: Grape seed, rooibos tea and olive leaf extracts demonstrated acute hypoglycemic benefits in adults with prediabetes and having less healthy metabolic profiles. A chronic study on the plant extracts is warranted to determine their longer-term impact on prediabetes. Trial Registration ID: ACTRN12617000837325
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    The Inhibitory Effects of New Zealand Pine Bark (Enzogenol®) on α-Amylase, α-Glucosidase, and Dipeptidyl Peptidase-4 (DPP-4) Enzymes.
    (MDPI (Basel, Switzerland), 12/04/2022) Lim WXJ; Gammon CS; von Hurst P; Chepulis L; Page RA
    The New Zealand pine bark extract (Enzogenol®) has previously been shown to elicit acute hypoglycaemic effects in humans. The present study investigated the underlying mechanisms of Enzogenol® in reducing postprandial glucose in humans. The potential inhibitory action of Enzogenol® against digestive enzymes: α-amylase and α-glucosidase, and dipeptidyl peptidase-4 (DPP-4) enzyme was determined. Enzogenol® demonstrated the ability to inhibit all three enzymes: α-amylase enzyme activity (IC50 3.98 ± 0.11 mg/mL), α-glucosidase enzyme activity (IC50 13.02 ± 0.28 μg/mL), and DPP-4 enzyme activity (IC50 2.51 ± 0.04 mg/mL). The present findings indicate the potential for Enzogenol® to improve postprandial glycaemia by delaying carbohydrate digestion via the inhibition of digestive enzymes (α-amylase and α-glucosidase), and enhancing the incretin effect via inhibiting the dipeptidyl-peptidase-4 enzyme. The inhibitory actions of Enzogenol® on enzymes should therefore be further validated in humans for its potential use in type 2 diabetes mellitus prevention and management.
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    A Narrative Review of Human Clinical Trials on the Impact of Phenolic-Rich Plant Extracts on Prediabetes and Its Subgroups
    (MDPI (Basel, Switzerland), 22/10/2021) Lim WXJ; Gammon CS; von Hurst P; Chepulis L; Page RA
    Phenolic-rich plant extracts have been demonstrated to improve glycemic control in individuals with prediabetes. However, there is increasing evidence that people with prediabetes are not a homogeneous group but exhibit different glycemic profiles leading to the existence of prediabetes subgroups. Prediabetes subgroups have been identified as: isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined impaired fasting glucose and glucose intolerance (IFG/IGT). The present review investigates human clinical trials examining the hypoglycemic potential of phenolic-rich plant extracts in prediabetes and prediabetes subgroups. Artemisia princeps Pampanini, soy (Glycine max (L.) Merrill) leaf and Citrus junos Tanaka peel have been demonstrated to improve fasting glycemia and thus may be more useful for individuals with IFG with increasing hepatic insulin resistance. In contrast, white mulberry (Morus alba Linn.) leaf, persimmon (Diospyros kaki) leaf and Acacia. Mearnsii bark were shown to improve postprandial glycemia and hence may be preferably beneficial for individuals with IGT with increasing muscle insulin resistance. Elaeis guineensis leaf was observed to improve both fasting and postprandial glycemic measures depending on the dose. Current evidence remains scarce regarding the impact of the plant extracts on glycemic control in prediabetes subgroups and therefore warrants further study.
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    Green kiwifruit: effects on plasma lipids and APOE interactions
    (28/05/2012) Gammon CS; Kruger R; Minihane AM; Conlon CA; von Hurst PR; Stonehouse W
    Background Diet is a crucial element in the reduction of risk of cardiovascular disease (CVD). Furthermore, response to dietary change may be influenced by genotype. Kiwifruit are a good source of several dietary components shown to improve dyslipidaemia and lower CVD incidence such as soluble fibre and some vitamins and phytochemicals. Objective To investigate the effect of consuming two green kiwifruit daily in conjunction with a healthy diet on plasma lipids and examine response according to apolipoprotein E (APOE) genotype in hypercholesterolaemic men. Design Eighty-five hypercholesterolaemic men (low-density lipoprotein cholesterol (LDL-C) >3.0 mmol/L and triglycerides (TG) <3 mmol/L) completed an eight week randomised controlled cross-over study, after undergoing a four week healthy diet phase. The study consisted of two 4-week treatment sequences of 2 green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Fasting blood samples were taken at baseline, 4 and 8 weeks for the measurement of plasma lipids (total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C)), serum apolipoproteins A1 and B (apoA1 and apoB). Outcomes After the kiwifruit intervention plasma HDL-C concentrations were significantly higher (mean difference 0.04 [95% CI: 0.01, 0.07] mmol/L [P=0.004]) and the TC/HDL ratio was significantly lower (0.15 [-0.24, -0.05] mmol/L [P=0.002]), compared to control. In carriers of APOE4 allele TG concentrations were significantly lower (0.18 [-0.34, -0.02] mmol/L [P=0.03]) after the kiwifruit intervention compared to control. There were no significant differences between the two treatments for plasma TC, TG, LDL-C and serum apoA1 or apoB. Conclusion The small but significant increase in HDL-C and decrease in TC/HDL ratio and TG (in APOE4 carriers) suggests that the regular inclusion of green kiwifruit as part of a healthy diet may be beneficial in improving the lipid profiles of men with high cholesterol. Source of Funding: ZESPRI® International Trial No: ACTRN12610000213044