Water-soluble polyphenol-rich clove extract lowers pre- and post-prandial blood glucose levels in healthy and prediabetic volunteers: an open label pilot study.

BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is a global pandemic, and contributes significantly to the increasing incidence of conditions such as cardiovascular disease (CVD). Postprandial plasma glucose measured 2-h after the start of a meal is a good indicator of the overall status of glucose homeostasis. Clove (Syzygium aromaticum L.) and its essential oils (eugenol and acetyl eugenol) have been shown in preclinical studies to modulate pathways involved in glucose homeostasis. In addition, a water-soluble polyphenolic extract of unopened clove buds was recently shown to benefit liver function and redox status. Therefore, we conducted an open-label pilot study to test whether this polyphenolic clove extract (PCE) could influence glucose metabolism. METHODS: We evaluated the effect of PCE supplementation (250 mg once daily for 30 days) on preprandial glucose levels and 2-h postprandial glucose levels in 13 otherwise healthy volunteers who were stratified into two groups according to their initial preprandial glucose levels: Group I (n = 7) ≤100 mg/dL, Group II (n = 6) - between 101 and 125 mg/dL. In an effort to elucidate the molecular mechanisms of PCE action, we tested in vitro the effects of PCE on glucose uptake, hepatocyte glucose production, and carbohydrate hydrolyzing enzymes. RESULTS: At day 12 of supplementation, we observed statistically significant reductions in mean postprandial glucose levels in both groups [(Group I: Initial - Day 12 PPG = 13.29 mg/dL, 95% CI: 3.329-23.24) (Group II: Initial - Day 12 PPG = 16.67 mg/dL, 95% CI: 4.687-28.65, P = 0.0159)], which continued through study completion at day 30. PCE supplementation significantly decreased mean preprandial glucose levels only in Group II at Days 24 (Initial - Day 24 = 13.00 mg/dL, 95% CI: 1.407-24.59, P = 0.0345) and 30 (Initial - Day 30 = 13.67 mg/dL, 95% CI: 5.766-21.57, P = 0.0067). In cell-based assays, PCE enhanced glucose uptake in L6 myocytes and inhibited hepatocyte glucose production HepG2 cells. In cell-free assays, PCE inhibited α-amylase activity and α-glucosidase activity. CONCLUSIONS: These findings underscore the therapeutic utility of PCE for maintaining healthy glucose metabolism and warrant further larger-scale clinical trials. TRIAL REGISTRATION: This trial was retrospectively registered in the ISRCTN registry on September 29, 2018 ( ISRCTN15680985 ).

Avoiding holiday seasonal weight gain with nutrient-supported intermittent energy restriction: a pilot study.

This pilot randomised controlled study evaluated the effects of a nutrient-supported intermittent energy restriction nutrition programme to prevent weight gain in healthy overweight adults during the 6-week winter holiday period between Thanksgiving and New Year. For 52 d, twenty-two overweight adults (mean age 41·0 years, BMI 27·3 kg/m2) were assigned to either the nutrition programme (n 10; two fasting days of 730 kcal/d (3050 kJ/d) of balanced shake and dietary supplements to support weight management efforts, followed by 5 d of habitual diet) or a control group (n 12; habitual diet). A significant weight loss from baseline (pre-holiday 10 d before Thanksgiving) to day 52 (post-holiday 3 January) was observed in the nutrition programme (75·0 (sd 9·8) v. 76·3 (sd 9·8) kg; P < 0·05). Body weight did not significantly change in the control group and there was no between-group difference. Increases from baseline in fasting insulin (42·9 %; P = 0·0256), updated homoeostasis model assessment (HOMA2) (43 %; P = 0·025), LDL-cholesterol (8·4 %; P = 0·0426) and total cholesterol (7·1 %; P = 0·0154) levels were also reported in the control group. In the nutrition programme group, baseline HDL-cholesterol and TAG levels measured after two fasting days increased (13 %; P = 0·0245) and decreased (22·8 %; P = 0·0416), respectively. There was no significant change in HOMA2. Between-group differences in changes in insulin levels (P = 0·0227), total cholesterol:HDL-cholesterol ratio (P = 0·0419) and HOMA2 (P = 0·0210) were significant. Overall compliance rate was 98 % and no severe adverse events were reported. These preliminary findings suggest that this intermittent energy restriction intervention might support weight management efforts and help promote metabolic health during the winter holiday season.

Kaempferia parviflora ethanol extract improves self-assessed sexual health in men: a pilot study.

BACKGROUND: Sexual health positively correlates with overall wellbeing. Existing therapeutics to enhance male sexual health are limited by factors that include responsiveness, adherence and adverse effects. As the population ages, safe and effective interventions that preserve male sexual function are needed. Published research suggests that various preparations of Kaempferia parviflora, a plant in the Zingiberaceae (ginger) family, support cardiovascular health and may ameliorate erectile function. OBJECTIVE: The aim of this study was to examine the effects of KaempMax™, an ethanol extract of the K. parviflora rhizome, on erectile function in healthy middle-aged and older men. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We conducted an open-label, one-arm study on 14 generally healthy males aged 50-68 years with self-reported mild erectile dysfunction, who were not using prescription treatments. Participants took 100 mg KaempMax™ daily for 30 days. MAIN OUTCOME MEASURES: Evaluations were conducted at baseline and on the final study assessment. Primary efficacy analyses included the International Index of Erectile Function (IIEF); secondary efficacy analyses included the Global Assessment Question about erectile function. RESULTS: Thirteen participants completed the 30-day study. Supplementation with KaempMax™ resulted in statistically significant improvements in erectile function, intercourse satisfaction and total scores on the IIEF questionnaire. KaempMax™ was well tolerated and exhibited an excellent safety profile. CONCLUSION: Our results suggest that KaempMax™ may improve erectile function in healthy middle-aged and older men. While the effects were not as pronounced as what might be seen with prescription medication, most participants found them satisfactory. Additional, longer and placebo-controlled clinical trials will be needed. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03389867.

Towards natural mimetics of metformin and rapamycin.

Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both). Four relatively unexplored compounds also scored well with rapamycin. This work revealed promising candidates for future experimental validation while demonstrating the applications of powerful screening methods for this and similar endeavors.

Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide.

Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4'-alkyl and 4'-alkoxy substituents afforded compounds exhibiting improved therapeutic index in rats with respect to liver triglyceride accumulation and enzyme elevation. Likely human metabolites of select compounds were prepared and characterized for their potential to inhibit MTP in vivo. Based on preclinical efficacy and safety data and its potential for producing short-lived, weakly active metabolites, compound 13 (PF-02575799) advanced into phase 1 clinical studies.