Cardiac is the number one killer. Here is what the evidence points to.

Blood pressure is tied to the balance of potassium and sodium and to the health of the vessel lining. In more than 10,000 US adults, higher sodium, lower potassium and a higher sodium-to-potassium ratio were each associated with higher blood pressure and hypertension odds. Pooling 32 randomized trials, higher potassium intake produced a dose-dependent reduction in blood pressure, and across 34 trials magnesium supplementation was associated with modest reductions.

The Adequate Intake today is 3,400 mg for men and 2,600 mg for women. In NHANES 2017-2018 only about a quarter of adults reached it, and in NHANES 2009-2010 average US intake was 2,640 mg against the 4,700 mg Adequate Intake then in force, with fewer than 1% of females and fewer than 25% of males reaching it on the reporting day.

The endothelial glycocalyx is a carbohydrate layer on blood vessel walls. It senses blood flow to trigger vasodilation, regulates vascular permeability and blood pressure, and works with the epithelial sodium channel as a shear stress sensor. High cholesterol, atherosclerosis and obesity break it down, and in 120 patients with atherosclerotic cardiovascular disease higher glycocalyx-shedding markers went with disease severity on coronary and carotid imaging.

ApoB-containing lipoproteins are the particles that carry cholesterol through the blood. Their retention and modification in the artery wall are crucial early events in atherosclerosis, and the wall they are trapped in is one where flow is low or turbulent and endothelial permeability and oxidative stress are increased.

Cholesterol is carried, and the harm is in the particle that has been oxidized in the wall. HDL protects by driving reverse cholesterol transport, removing excess cholesterol from tissues for excretion via the liver and bile, while atherosclerosis is driven by oxidized LDL particles in the artery wall, which macrophages take up to form foam cells.

The trials on file measured cholesterol markers directly. In a 5-week trial of 39 healthy adults, gamma-tocopherol at 100 mg a day reduced LDL cholesterol; vitamin C at 1,000 mg a day improved cholesterol and endothelial function markers in diabetic patients; and in a 12-month study of 1,062 people taking nattokinase, lipid and artery measures improved.

Higher dietary and serum magnesium were each associated with lower risk of cardiovascular events in a meta-analysis of 19 prospective cohorts. Higher potassium intake was linked with a 24% lower stroke risk across 22 randomized trials, a higher sodium-to-potassium ratio went with a 10% higher risk of cardiovascular events across 24 studies, and higher dietary menaquinone intake went with 57% lower coronary heart disease mortality over 10 years in 4,807 adults.

Vitamin E is a family of molecules. Alpha-tocopherol is a chain-breaking antioxidant, and 800 IU a day increased LDL oxidation resistance in healthy adults. A gamma-tocopherol-rich supplement improved brachial artery flow-mediated dilation in young smokers, and 84% of US adults fell below the estimated average requirement for vitamin E in NHANES 2005-2016.

In a clinical study, nattokinase decreased plasma fibrinogen, factor VII and factor VIII in human subjects without significant adverse events. Nattokinase and vitamin K2 both act on clotting, and vitamin K interacts with warfarin. Nattokinase, vitamin K2 and high-dose vitamin E are the three in this stack that interact with blood thinners, so anyone on a blood thinner tells the prescriber who manages it before adding any of them.

The trials measured how fast calcium builds up in the coronary arteries, and K2 slowed it. A meta-analysis found vitamin K2 slowed coronary calcification progression, a two-year placebo-controlled trial of menaquinone-7 found roughly 29% less progression of coronary artery calcification, and in 398 patients with severe coronary artery calcification, 24 months of vitamin K2 plus D3 reduced calcium score progression versus placebo.

What is on the plate has changed, and a blood test reads what circulates, not what is inside the cells. USDA records for 43 garden crops showed declines in several minerals and in protein between 1950 and 1999, intracellular potassium deficiency can occur despite a normal serum potassium, and serum magnesium, under 1% of body stores, can look normal despite depletion.

Potassium regulates cell membrane potential and controls sodium reabsorption in the kidney's distal nephron. Higher dietary potassium was associated with lower odds of chronic kidney disease across 104 studies, and higher urinary potassium excretion with slower age-related decline in kidney function.