Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways.

A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being. Flavonoids, for example, have effects on skeletal muscle, adipocytes, liver, and pancreas, and myocardial, renal, and immune cells, for instance, related to 5'-monophosphate-activated protein kinase phosphorylation, endothelial NO synthase activation, and suppression of NF-κB (nuclear factor-κB) and TLR4 (toll-like receptor 4). Effects of dairy are similarly complex and may be mediated by specific amino acids, medium-chain and odd-chain saturated fats, unsaturated fats, branched-chain fats, natural fats, probiotics, vitamin K1/K2, and calcium, as well as by processing such as fermentation and homogenization. These characteristics of dairy foods influence diverse pathways including related to mammalian target of rapamycin, silent information regulator transcript-1, angiotensin-converting enzyme, peroxisome proliferator-activated receptors, osteocalcin, matrix glutamate protein, hepatic de novo lipogenesis, hepatic and adipose fatty acid oxidation and inflammation, and gut microbiome interactions such as intestinal integrity and endotoxemia. The complexity of these emerging pathways and corresponding biological responses highlights the rapid advances in nutritional science and the continued need to generate robust empirical evidence on the mechanistic and clinical effects of specific foods.