The Problem
Cardiovascular disease is caused by chronic low-level inflammation (1, 2).  The ultimate cause is a pro-inflammatory diet.  The consequences of such a pro-inflammatory diet leads to the build-up of atherosclerotic lesions, the rupture of those lesions, and an inability to repair damaged tissue to maintain an efficient cardiovascular system. 

The Traditional Medical Approach
Drugs (such as statins) that lower cholesterol are the primary drugs currently used to treat heart disease.  Statins are known to activate AMPK, which also inhibits cholesterol synthesis (3,4).  Thus, statins could be considered to be AMPK-activating drugs.  Cardiovascular disease is also correlated with increased oxidative stress (5).  Finally, cardiovascular disease is highly associated with insulin resistance (6).

The Metabolic Engineering® Approach
The molecular drivers of cardiovascular disease can be attenuated by consistent use of Metabolic Engineering®.  The Zone diet component activates AMPK due to calorie restriction (7).  The omega-3 fatty acid component reduces inflammation and increases its resolution (8).  Finally, the polyphenols reduce oxidative stress (5). 

Thus, Metabolic Engineering® works in concert with any drug therapy for cardiovascular treatment to help reprogram your metabolism by activating AMPK.  Activation of AMPK decreases cholesterol synthesis, reduces inflammation, increases resolution, and decreases oxidative stress by increasing Nrf2 activity.  The overall effect is a decrease in insulin resistance as well as the level of cellular senescence. These benefits of Metabolic Engineering® either make a cardiovascular drug work better or allow the physician to potentially reduce the amount of drug to manage their patient’s cardiovascular disorder with fewer side effects.

References
1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002; 105(9):1135-43. doi: 10.1161/hc0902.104353.

2. Soehnlein O and Libby P. Targeting inflammation in atherosclerosis – from experimental insights to the clinic.  Nat Rev Drug Discov. 2021; 20:589-610.doi: 10.1038/s41573-021-00198-1.

3. Dehnavi S, Kiani A, Sadeghi M, Biregani AF, Banach M, Atkin SL, Jamialahmadi T, Sahebkar A. Targeting AMPK by Statins: A potential therapeutic approach.Drugs. 2021; 81:923-933. doi: 10.1007/s40265-021-01510-4.\

4. Foretz M, Viollet B. Measurement of AMPK-induced inhibition of lipid synthesis flux in cultured cells. Methods Mol Biol. 2018; 1732:363-371. doi: 10.1007/978-1-4939-7598-3_23.

5. Cheng YC, Sheen JM, Hu WL, Hung YC.  Polyphenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke.  Oxid Med Cell Longev. 2017; 2017:8526438. doi: 10.1155/2017/8526438. 

6. Kosmas CE, Bousvarou MD, Kostara CE, Papakonstantinou EJ, Salamou E, Guzman E.  Insulin resistance and cardiovascular disease.   J Int Med Res. 2023; 51: 3000605231164548. doi: 10.1177/03000605231164548.

7. Guo Z, Wang M, Ying X, Yuan J, Wang C, Zhang W, Tian S, Yan X. Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT₁-PGC_1a energy metabolism pathway.  Sci Rep. 2023, 13:2045. doi: 10.1038/s41598-023-27611-6.

8. Back M, and Hansson GK. Omega-3 fatty acids, cardiovascular risk, and the resolution of inflammation. FASEB J. 2019; 33:1536-1539. doi: 10.1096/fj.201802445R.