Cardiovascular health is influenced by modifiable factors that include inflammatory status. Abnormal inflammatory responses that lead to chronic inflammation are associated with the development and progression of many cardiovascular-related pathologies. 

During the process of endothelial cell damage, oxidative stress, and inflammatory responses are interconnected. The activity of reactive oxygen species (ROS) is linked to many inflammatory pathways that influence endothelial health and vascular function.

During the inflammatory process, endothelial cells undergo major changes, which include:

• Increased expression of proinflammatory mediators
• Increased permeability of plasma proteins into the vasculature
• Activation and increased prevalence of adhesion molecules

The nuclear factor-κB (NF-κB) pathway is one of the most important elements in the discussion on the inflammatory response and the increased expression of proinflammatory mediators. Increases in ROS activity can lead to NF-κB activation. After activation, NF-κB targets molecules associated with endothelial cell dysfunction. These include the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6; these in particular are often involved in cardiovascular diseases (CVDs) and certain metabolic-related illnesses. TNF-α, IL-1β, and IL-6 have also been linked to endothelial monocyte infiltration and insulin resistance. TNF-α has also been associated with the degradation of the endothelial glycocalyx (EGX). The EGX is a thin gel-like layer that lines every blood vessel in the body, acting as the first line of defense in vessel walls. NF-κB also activates cell adhesion molecules including vascular cell adhesion protein-1 (VCAM-1). Research suggests that many micronutrients can help support the modulation of NF-κB, the inflammatory response, and oxidative stress. 

Certain foundational vitamins and minerals may help support inflammatory status and endothelial health. Vitamin D, for instance, plays a role in cardiovascular and metabolic health and may help promote antioxidative status and a normal inflammatory response. Evidence from clinical and epidemiological studies suggests a potential connection between suboptimal vitamin D status and hypertension.  Improvements in inflammatory markers including hs-CRP, IL-1β, and NF-κB have been observed in the presence of vitamin D supplementation in individuals with certain cardiometabolic illnesses. 

In addition, magnesium is involved in the synthesis of glutathione and may help protect against oxidative stress, a known contributor to atherogenesis and other CVDs. Research indicates that magnesium may also help support a normal inflammatory response through its ability to help modulate NF-κB and the expression of certain pro-inflammatory cytokines.

Evidence suggests that rhamnan sulfate, a micronutrient derived from the marine plant Monostroma nitidum, may help support the barrier integrity of endothelial cells and act as an inhibitor of NF-κB pathway activation induced by TNF-α. Preliminary studies suggest that rhamnan sulfate may also help support the prevention of the degradation of the EGX and the potential deposition of low-density lipoprotein-c (LDL-c).

Alpha-lipoic acid (ALA) is a molecule found in the mitochondria of cells and has been shown to help support antioxidative status, a normal inflammatory response, cardiovascular function, and healthy metabolism. Research indicates it may help modulate the activity of certain pro-inflammatory cytokines such as NF-κB. It can scavenge ROS and exhibit chelating activity for certain metals. Animal studies suggest that ALA may help support normal blood pressure, although the evidence is preliminary.

While more research is needed, evidence suggests that certain micronutrients, vitamins, and minerals may help promote endothelial health. They may also help support antioxidative status and a healthy inflammatory response.

By Dr. Cory Ambrose, ND, MAT