Events linking diet and disease

Cardiovascular death occurs with thrombosis and arrhythmia, often after years of progressive vascular inflammation. Two chronic dietary imbalances lead to these conditions: excess food energy intake over expenditure and excess intake of omega-6 (n-6) over omega-3 (n-3) fats. Each imbalance can be readily prevented.

Meals with excess food energy increase production of plasma triglycerides (fats) which circulate and form non-esterified fatty acids (NEFA) that stress vascular walls. In addition, unburned sugar and fat increase cytosolic levels of acetyl-CoA, HMG-CoA and mevalonate and lead to prenylated proteins that impair beneficial nitric oxide actions and increase inflammatory/proliferative vascular events. Nitroglycerin provides nitric oxide to impaired vessels and aspirin cuts n-6 eicosanoid-driven thrombosis.. Plasma cholesterol is more a marker of excess mevalonate than a mediator of vascular injury, and statin has anti-inflammatory action by inhibiting mevalonate formation. The medications treat events driven by the two readily prevented nutritional imbalances in the upper left of the figure.

Chronic dietary shortages of n-3 fats create high proportions of n-6 highly unsaturated fatty acids (HUFA) in tissue phospholipids that enhance the intensity of n-6 eicosanoid-mediated inflammation, thrombosis and arrhythmia. Eating less food energy per meal and eating more n-3 and less n-6 fats are useful primary steps for preventing risk. To see slide show of the above image please select the following link: Chain of Events