The effect of 8 plant extracts and combinations on post-prandial blood glucose and insulin responses in healthy adults: a randomized controlled trial.

BACKGROUND: Lower post-prandial glucose (PPG) and insulin (PPI) responses to foods are associated with reduced diabetes risk and progression. Several plant extracts have been proposed to reduce PPG or PPI by inhibiting enzymes or transporters involved in carbohydrate digestion and uptake. This study evaluates a range of such extracts, consumed with a carbohydrate load, for their effects on PPG, PPI and indicators of (gastrointestinal) tolerance. METHODS: Interventions were extracts of mulberry fruit (MFE, 1.5 g), mulberry leaf (MLE, 1.0 g), white bean (WBE, 3.0 g), apple (AE, 2.0 g), elderberry (EE, 2.0 g), turmeric (TE, 0.18 g), AE + TE, and EE + TE. Each of these 8 individual extracts or combinations were added to a rice porridge containing ~ 50 g available carbohydrate (control). In a within-subject (randomised, balanced incomplete block) design, individual subjects received the control and a subset of 4 of the 8 extracts or combinations. Participants were 72 apparently healthy adults (mean [SD] age 31.2 [5.5] yr, body mass index 22.1 [2.0] kg/m2). The primary outcome was the percentage change in 2-h PPG (positive incremental area under the curve) relative to control. Secondary measures were the 2-h PPI response, 7-h breath hydrogen, measures of gastrointestinal discomfort, and urine glucose. RESULTS: In the 65 subjects who completed the control and at least one intervention treatment, additions of AE, MFE and MLE produced statistically significant reductions in PPG vs control (p < 0.05; mean effect - 24.1 to - 38.1%). All extracts and combinations except TE and WBE significantly reduced PPI (p < 0.01; mean effect - 17.3% to - 30.4%). Rises in breath hydrogen > 10 ppm were infrequent, but statistically more frequent than control only for MLE (p = 0.02). Scores for gastrointestinal discomfort were extremely low and not different from control for any treatment, and no glucosuria was observed. CONCLUSIONS: Additions of AE, MFE and MLE to rice robustly reduced PPG and PPI. EE significantly reduced only PPI, while TE and WBE showed no significant efficacy for PPG or PPI. Breath hydrogen responses to MLE suggest possible carbohydrate malabsorption at the dose used, but there were no explicit indications of intolerance to any of the extracts. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04258501. Registered 6 February 2020 - Retrospectively registered.

LDL-Cholesterol Lowering of Plant Sterols and Stanols-Which Factors Influence Their Efficacy?

The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is summarized in several meta-analyses showing a dose-response relationship with intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes evidence for the impact of various factors potentially influencing the LDL-C-lowering efficacy of PSS. PSS are efficacious in all food formats and in food supplements. Some factors related to food format, e.g., solid vs. liquid foods, seem to impact efficacy, while there is no difference between free PSS and esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially in the morning with light breakfast, leads to a sub-optimal LDL-C lowering. However, intake frequency seems influenced by intake occasion, i.e., with or without a meal, and time of day. Meal intake is a critical factor for an optimal LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to influence the LDL-C lowering effect of PSS with greater reductions reported for men than women; but overall evidence is inconclusive and larger studies show no gender by treatment interaction. In conclusion, PSS are efficacious in all foods and food supplements; for optimal efficacy they should be consumed with a (main) meal and twice daily.

Molecular structures of citrus flavonoids determine their effects on lipid metabolism in HepG2 cells by primarily suppressing apoB secretion.

This study investigated the underlying mechanisms of action for blood lipid lowering effects of citrus flavonoids and their methoxylated analogues (n = 19; dose range: 0-100 µM) in HepG2 cells. Cholesterol (CH) and triglyceride (TG) syntheses were assessed by measuring the incorporation of (14)C-acetate and (14)C-glycerol, respectively, whereas apoB secretion was determined by ELISA. Results show that two polymethoxylated citrus flavonoids (PMFs), tangeretin and nobiletin, potently inhibited apoB secretion (IC(50) = 13 and 29 µM, respectively) and modestly inhibited CH synthesis (IC(50) = 49 and 68 µM) and TG synthesis (IC(50) = 14 and 73 µM), without effecting LDL-receptor activity. Other PMFs (e.g., sinensetin) and non-PMFs (e.g., hesperetin and naringenin) had only weak effects on CH and TG syntheses and apoB secretion (IC(50) > 100 µM). The structure-activity analysis indicated that a fully methoxylated A-ring of the flavonoid structure was associated with a potent inhibitory activity on hepatic apoB secretion. In conclusion, this study using HepG2 cells indicates that citrus flavonoids with a fully methoxylated A-ring may lower blood CH and TG concentrations primarily by suppressing hepatic apoB secretion as a main underlying mode of action.

Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters.

Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

Theaflavins from black tea, especially theaflavin-3-gallate, reduce the incorporation of cholesterol into mixed micelles.

Tea is one of the most widely consumed beverages in the world and may be associated with reduced heart disease rates. Theaflavins, which are formed in the production of black tea, have been suggested being responsible for the blood-cholesterol-lowering (BCL) effects of tea. We hypothesized that the effect of theaflavins on BCL could be through interference in the formation of dietary mixed micelles, which could result in reduced intestinal cholesterol absorption. Micelles were produced by mixing oleic acid, bile acids, lyso-phosphatidylcholine, and cholesterol. Theaflavin-treated micelles/particles were analyzed using electron microscopy (cryo-TEM), high-performance liquid chromatography (HPLC) analysis, and light-scattering particle size measurements. A dose-dependent inhibitory effect of theaflavins on the incorporation of (14)C-labeled cholesterol into micelles and a theaflavin-dependent increase in particle size was found. These particles consisted of insoluble large multilamellar vesicles with onion-like structures. Ultracentrifugation and HPLC analysis revealed that the pellets contained mainly theaflavin-3-gallate, while the remaining theaflavins were found to be present in the supernatant. Using purified theaflavin subtypes confirmed that mainly theaflavin-3-gallate is responsible for multilamellar vesicle formation. These results show that theaflavins can play a role in decreased intestinal cholesterol absorption via inhibition of micelle formation.