The prevalence and mortality due to multifactorial polygenic diseases; hypertension, coronary artery disease (CAD), diabetes and cancer vary depending upon genetic susceptibility and environmental precursors because they have identifiable mendelian subsets. Rapid changes in diet and lifestyle, may influence heritability of the variant phenotypes that are dependent on the nutraceutical or functional food supplementation for their expression. It is possible to recognize the interaction of specific nutraceuticals, with the genetic code possessed by all nucleated cells. There is evidence that South Asians have an increased susceptibility to CAD, diabetes mellitus, central obesity and insulin resistance at younger age, which may be due to interaction of gene and nutraceutical environment. These populations appear to have enherited predisposition and may have interaction of internal nutritional status and environmental factors. Higher intake of refined starches and sugar increases generation of super oxide anion in the leucocytes and mononuclear cells, and free fatty acids (FFA), as well as higher amount and activity of nuclear factor-kB (NF-kB), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. Glucose intake also causes an increase in two other proinflammatory transcription factors; activating protein-1 (AP-1) and early growth response protein-1 (Egr-1), the first regulating the transcription of matrix metallo-proteinases and the second modulating the transcription of tissue factor and plasminogen activator inhibitor-1. Refined food, mixed meal induces activation of NF-kB associated with free radicals generation by mononuclear cells. The super oxide anion is an activator of at least two major pro-inflammatory transcription factors, NF-kB and AP-1. Increased intake of linoleic acid, saturated fat, trans fat and refined starches and sugars can increase the generation of free radicals and activate the NF-kB, leading to rapid expression of proinflammatory genes. It is possible that nutraceuticals; antioxidants, micronutrients, minerals, vitamins, coenzyme Q10 and w-3 fatty acids may inhibit the generation of super oxide and suppress NF-kB as well as AP-1, and Egr-1 leading to suppression of phenotypic expressions. It is known that genes are important in determining enzymes, receptors, cofactors, structural components involved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining individual risk for vascular diseases and diabetes. It seems that these phenotypic expressions may be silenced by targeting simple sequence differences known as single nucleotide polymorphisms by nutraceuticals and slowly absorbed wild foods rich in micronutrients and antioxidants.