Table 3.

Summary: capsaicinoids modulating CMS risk factors through different potential mechanism of action.

CMS markers	Potential mechanism of action∗
Control of IGT/diabetes	Reducing carbohydrate absorption, improving insulin sensitivity, improving glucose utilization and metabolism, delaying glucose absorption, increase in fecal excretion of acidic sterols, decreasing fasting and postprandial hyperglycemia and improving glycemic control, increasing blood flow to insulin-sensitive tissues, adipose tissue lipolysis, and the catabolism of glucose and fatty acids but inhibiting fatty acid synthesis, and ameliorating oxidative stress [26, 39, 40]
Reduction of dyslipidemia	Antilipidemic effects: binding bile acids and inhibiting pancreatic lipase; plasma lipids, functionality of aorta including atherosclerotic plaque development, cholesterol absorption biomarker, mRNA levels of hepatic 3-hydroxyl-3-methylglutaryl CoA reductase, and cholesterol-7α-hydroxylase were downregulated; upregulation of cholesterol 7α-hydroxylase and downregulation of liver X receptor alpha, inhibiting LDL-cholesterol oxidation, fecal sterol excretion, and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism, inhibiting the hepatic cholesterol synthesis [53, 64–72]
Reduction of hypertension	Antihypertensive effects: direct vasodilators, calcium channel blockers, inhibiting the gene expression of COX-2, controlling the vascular tone through the release of calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A, increase in intracellular calcium, which causes the release of several neuropeptides [53–63]
Attenuating body weight	Increased energy expenditure, increased lipid oxidation, reduced appetite, reduced abdominal adipose tissue levels, decreased body fat, pad weights of epididymal and prerenal adipose tissues, and reduced fat accumulation by downregulating PPARγ and C/EBPα in 3T3Li adipocytes [28, 49, 72]
Improving endothelial function	Improving endothelial function, inhibiting the transmembrane influx of calcium ions into cardiac and vascular smooth muscle, improving coronary vascular circulation, and decreasing expression of TRPV1 and cation influx [73–75]
Reduction in inflammation	Anti-inflammatory effects: lowering cytokines and C-reactive protein, reducing eNOS transcription, and depleting neurons of neurotransmitters, leading to reduction in pain sensation and blockade of inflammation [76–82]

^∗Studies based on in vitro and in vivo studies and few human studies.