The invention encompasses compositions and methods for effectively interfering, reducing and preventing conversion of 
vascular smooth muscle cells (VSMCs) and circulating stem cells to osteoblastic bone-like cells, thereby reducing and / or preventing 
vascular calcification (VC) or 
calcium mineral (hydroxyapatite) deposition in the vasculature. The severity and extent of 
calcification in the major arteries reflect atherosclerotic plaque burden and strongly predict cardiovascular morbidity and mortality. The present inventive compositions used for administration to human and other mammalian subjects comprise select actives that inhibit, interfere or regulate the biochemical processes leading to such 
calcification and include (1) at least one agent that modulates expression and / or activity of 
peroxisome activated 
protein receptor gamma (PPAR-γ); (2) at least one agent that inhibits expression and / or suppresses activity of one or more of the osteogenic transcription factors (Cbfα1 / Runx2, Osterix, Msx2) and β-
catenin signaling; (3) at least one agent that inhibits expression and / or suppresses activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4), 
alkaline phosphatase (ALP), and 
osteocalcin; (4) at least one agent that inhibits the activity of 
Reactive Oxygen Species (ROS); and (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and 
prostaglandin E2 (PGE2). The compositions may further comprise at least one agent that promotes expression and / or 
carboxylation of matrix Gla 
protein (MGP). Advantageously, these select actives include materials such as phytonutrients, vitamins and minerals that have been broadly used in food and drink products and are safe for human and pet / animal consumption. Compositions with such combinations have the ability to prevent, treat and reverse VC not only in 
coronary arteries but also in other tissues capable of undergoing undesirable 
calcification. In addition the present compositions are effective against associated conditions or contributory factors / inducers to VC, including diabetes, 
obesity, hypertension, 
inflammation, 
oxidative stress, 
osteoporosis and 
arthritis.