Ayurvedic Herbal Preparation Supplementation Does Not Improve Metabolic Health in Impaired Glucose Tolerance Subjects; Observations from a Randomised Placebo Controlled Trial.

The increased usage of alternative Ayurvedic treatments as potential health-beneficial therapies emphasizes the importance of studying its efficacy in sound placebo-controlled intervention trials. An example of such a traditional Ayurvedic herbal preparation is Mohana Choorna, a mixture composed of 20 different herbs and used to prevent and treat type 2-diabetes (T2D). We studied the efficacy of "Mohana Choorna" on T2D-related parameters in subjects with impaired glucose tolerance. In a double blind, placebo-controlled cross-over trial, 19 overweight (BMI > 27 kg/m2) subjects aged 50-70 years with an impaired glucose tolerance received two four-week interventions, i.e., herbal or placebo with a four-week wash-out between interventions. HbA1c, glucose, insulin, triglycerides, cholesterol, blood pressure and augmentation index were measured before and after both interventions at fasting and during a glucose tolerance test. After both interventions, urine was collected to measure treatment exposure using LCMS-based metabolomics and whole genome gene-expression in adipose tissue of 13 subjects. The herbal intervention did not affect plasma glucose triglycerides, cholesterol, blood pressure or the augmentation index but showed a trend towards an increased insulin, HOMA-IR and postprandial insulin levels (p = 0.054, p = 0.056 and p = 0.095 respectively). An increase in expression of inflammation-related gene sets in adipose tissue was observed after the herbal intervention compared to placebo. Urine metabolomic analysis did not reveal a correlation of the presence of specific plant metabolites with "health markers". Our findings suggest that there is no substantiating evidence to claim that four weeks' use of the Ayurvedic herbal supplement Mohana Choorna beneficially affects glucose homeostasis.

Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial.

Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.

Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention.

SCOPE: People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish-oil intervention. METHODS AND RESULTS: Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only. CONCLUSION: The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish-oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN-related genes.