Bodybuilders, particularly those with excess muscle tissue and higher-than-normal body masses, must pay careful attention to their biomarkers in order to prevent adverse events. Most bodybuilders seem to intuitively understand the importance of things like liver and kidney function—even cholesterol and blood pressure—because these things have tighter feedback loops (i.e., if blood pressure is unduly elevated, or liver enzymes are off the charts, the consequences are more immediate). That said, cardiovascular disease, the sum total of all possible cardiac and circulatory risk factors, is of utmost importance for the aspiring physique athlete—or anyone looking to optimize their overall health. One doesn’t need to be a bodybuilder to want to forestall the leading cause of death in America (CVD). It is with these considerations in mind that Dynamic Evolution formulated Heart Pill.
Vitamin D3 (as cholecalciferol) (5,000IU) - without getting into specific mechanisms, vitamin D is generally cardioprotective—particularly if your serum levels are less than 30ng/dL. Vitamin D3 directly opposes parathyroid hormone [PMID: 28272298]. Parathyroid hormone can be thought of as an adaptive, even inflammatory, hormone that primarily senses low blood calcium and pulls it out of bone stores to redress the shortage. Keeping parathyroid hormone low will keep calcium locked away in bones where it belongs—not in circulation where it may form arterial plaques. Vitamin D3 has also been shown to lower RBC count, hematocrit, and erythrocytes [PMID: 26621634]. These markers are of utmost importance for bodybuilders (or anyone using certain pharmaceuticals) as a common issue they face is increased clotting risk. Finally, Vitamin D can prevent hypertension in, at the very least, those who are deficient in it [PMID: 35737199].
Vitamin K2 (as Menaquinone-7) (200mcg) - Vitamin K deficiency causes excess calcification and therefore arterial stiffness [technically, it causes a deficiency of a crucial inhibitory protein that blocks calcification of Matrix Gla protein (MGP) is a member of a family of vitamin K2 dependent, Gla-containing proteins]. MGP has a high affinity binding to calcium ions, similar to other Gla-containing proteins. The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. Interestingly, in bones, MGP’s production is increased by none other than vitamin D (the first ingredient in Heart Pill). Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP, which requires vitamin K-dependent activation, is a potent locally acting inhibitor of arterial calcification. An easy way to understand vitamin K’s function is as a “traffic cop,” directing cars (calcium) out of soft tissues (blood vessels, organs) and into bones and teeth. Therefore, vitamin K can be understood to improve health outcomes by lowering blood pressure in the short-term and in the long-term, by preventing arterial calcification. Lastly, we chose MK-7 (Menaquinone-7, the “7” refers to the number of isoprenyl units in the side chain of the parent molecule) because it has a rich dietary history (MK-7 is primarily found in fermented foods such as Japanese natto) and superior absorption and half-life [PMID: 27976475]. It should be noted, too, that the Japanese population are renowned for their long lives and (comparative) lack of heart disease.
Odorless Garlic Extract (1% Alliin) (600mg) - A curious property of alliin (S-Allyl-L-cysteine sulfoxide) is while it exists in wild garlic, the moment the garlic is macerated (chewed), or chopped, crushed, or cooked, there is an intrinsic enzyme in the garlic called alliinase that converts alliin into allicin, which is unstable. Orally administered alliin, however, was found to be absorbed intact and to reach plasma and liver without being converted to allicin so we’ve chosen it to include in Heart Pill. Alliin and other aged garlic extracts (AGEs) exhibit strong evidence for cardiovascular protection via four main mechanisms:
Garlic and garlic-derived organosulfur compounds such as alliin (S-Allyl-L-cysteine sulfoxide) have been found to decrease the synthesis of cholesterol by hepatocytes [PMID: 8972460]. Garlic-derived organosulfur compounds, including S-allylcysteine (this is alliin), have been found to inhibit HMG-CoA reductase, a critical enzyme in the cholesterol biosynthesis pathway [PMID: 12042421].
Garlic-derived organosulfur compounds such as alliin inhibit platelet aggregation in the test tube [PMID: 16484563]. Aged garlic extract (AGE) inhibits artificially stimulated platelet aggregation by downregulating the fibrinogen binding activity of glycoprotein (GP) IIb/IIIa fibrinogen receptor found on platelets [PMID: 23069586]. This same GP IIb/IIIa receptor is the target of several anticoagulant drugs such as abciximab. It is thus that garlic exhibits its renowned ability as a blood thinner.
The proliferation of normally quiescent VSMCs is a hallmark of vascular disease(s), including atherosclerosis and coronary restenosis (the recurrence of abnormal narrowing of an artery or valve after corrective surgery) [PMID: 15361792]. Preliminary evidence suggests that organosulfur compounds from garlic could inhibit the proliferation and migration of VSMCs [PMID: 11238806].
Elevated oxidized low-density lipoprotein (ox-LDL, the “bad” cholesterol) concentration in plasma is thought to be a crucial driver in the pathogenesis of atherosclerosis. Oxidized LDL stimulates recruitment of inflammatory white blood cells (macrophages, sometimes referred to as foam cells) from the blood to the arterial wall by inducing the expression of vascular cell adhesion molecules. Compounds downstream from alliin/allicin, including diallyl disulfide (DADS), and diallyl sulfide (DAS), inhibited the expression of these adhesion molecules on endothelial cell surface by reversing ox-LDL-induced inhibition of PI3K/Akt and cAMP responsive element binding protein (CREB) signaling pathways [PMID: 18492825].
Olive Leaf Extract (20% Oleuropein) (500mg) - Olive phenolics in general, which are present in high levels in olive leaf supplements, appear to potently protect against the oxidation of LDL cholesterol. If you recall from the garlic section above, ox-LDL is a necessary prerequisite of arterial plaque formation. In other words, this is a vital process to inhibit. Oleuropein consists of a molecule of elenolic acid linked to the orthodiphenol hydroxytyrosol by an ester bond, and to a molecule of glucose by a glycosidic bond [PMID: 23964170]. This seemingly trivial point is raised here for a specific reason: some of the protective effects of olive phenolics are ascribed to tyrosol/hydroxytyrosol (rather than oleuropein), but oleuropein contains those compounds. Oleuropein, then, is the most broadly protective phenolic compound found in olive oil.
Some compounds present in olive leaf possess ACE inhibiting properties, which is a well-documented mechanism for reducing blood pressure. There is a compelling crossover twin study [PMID: 18729245] that shows a reduction in blood pressure comparable to Captopril, a prescription ACE-inhibitor.
Oleuropein also appears to have the ability to lower triglycerides. This may derive from its antioxidant properties or its anti-diabetic properties, as olive leaf extracts exert protective effects on glucose metabolism [PMID: 22512698].
Oxyjun® [Terminalia Arjuna Extract (bark)] (400mg) - Oxyjun® is an aqueous extract of Terminalia arjuna, removed using a hydrothermal process (water at a specific temperature and pressure), which includes a matrix of bioactives including polyphenols and glycosides. It helps support overall heart health and can also reduce fatigue, both literally (via cardiac efficiency, see below) and perception of fatigue (based on a questionnaire). Oxyjun® helps enhance cardiovascular function and endurance in both healthy, young exercising adults, as well as supports heart health and reduces physical fatigue in all adults (regardless of activity level). Research shows that aqueous extracts of T. arjuna help increase myocardial contractility (i.e., the ability of the heart muscle to beat harder and more effectively). Oxyjun® specifically supports heart health by increasing the Left Ventricular Ejection Fraction. This can lead to a greater volume of blood flow through the heart, which results in greater blood flow from the heart to the body, and may enhance oxygenation and nutrient delivery to cells. It is via the above mechanisms that Oxyjun® lowers blood pressure.
Green Tea (Camellia sinensis) Extract (as CellFlo6™) (300mg) - Green tea catechins have been studied extensively for their effects on cardiovascular, immune, and metabolic health as well as weight management. CellFlo6™ is created using a double-extraction process that increases catechins, specifically galloylated procyanidins, which are believed to contribute to its high performance and muscle recovery properties. Specifically, CellFlo6™ is a proprietary blend of gallate-enhanced oligomers, consisting of dimers, trimers, tetramers and pentamers derived from green tea, that stimulate nitric oxide production, induce vasodilation, and promote vasorelaxation. Moreover, CellFlo6™ counteracts endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells [PMID: 26956245]. Inhibition of a peptide that itself inhibits nitric oxide results in net greater nitric oxide bioavailability [PMID: 19887561].