Flow-Mediated Dilation, Nutrition, and the Endothelium

Endothelium, the thin layer of cells that separate blood vessel walls and the circulating blood, is more than a structural barrier. These cells represent a dynamic, responsive, generally adaptive, and complex organ system. Emerging research suggests diet and nutrition have a significant impact on its function and subsequent effects on health and disease. Today, there are valuable noninvasive measurement techniques or biomarkers for endothelial function, especially elasticity or compliance.

An active regulatory organ, the endothelium monitors the hemodynamic, humoral, and inflammatory signals to which it is exposed by the blood and responds by secreting factors that affect vessel tone and structure. Only one cell layer in thickness, the endothelium controls vasomotor tone, trafficking of nutrients, maintenance of blood fluidity, and growth of new blood vessels throughout the body’s organ systems.

When blood flow increases through a vessel, a healthy vessel dilates—a phenomenon known as flow-mediated dilation (FMD). It is generally measured in the large-diameter brachial artery in the upper arm. Thus, this is the blood vessel that is amenable to placement of a blood pressure cuff. Once stable systolic and diastolic pressures are achieved, images of the brachial artery can be obtained by ultrasound. The blood flow can then be calculated. Endothelial dysfunction is reflected by an impaired FMD response. Impaired responses are typically observed in those with cardiovascular disease and symptoms of vascular inflammation and among those consuming select dietary substances that are pharmacologically active. Such substances include caffeine, sodium, and flavanols.

It has long been known that a variety of other stimuli acutely influence FMD. These include a single calorie-dense meal, psychological stress (mediated by neuropeptides and catecholamines), circulating levels of estrogen and progesterone, smoking, acute changes in glucose, and changes in electrolytes (such as sodium and potassium). Thus, FMD may be a novel biomarker and valuable proxy for endothelial dysfunction. FMD is also a tool to assess response to therapeutic interventions, including diet and medications.

A number of reports have documented the impact of specific components of diet on FMD. Shechter et al. (2011) reported that caffeine ingestion significantly improved endothelial function as reflected in FMD and lowered plasma levels of markers of inflammation in subjects with and without coronary artery disease. Heiss et al. (2007) observed sustained FMD improvement among smokers consuming single doses of flavanol (28–918 mg flavanol) cocoa drink.

Harris et al. (2011) linked vitamin D supplementation with improved endothelial function in African-American subjects. Similarly, it has been known for some time that vitamin E supplementation attenuated transient impairment of endothelial function in smokers (Neunteufl et al., 2000). Most impressive is a recent report by Mavri et al. (2011) that demonstrated significant improvement in FMD with the non-pharmacologic intervention of a reduced-calorie/weight reduction diet.

It is worth noting the blood-brain barrier, the remarkable endothelial separation of circulating blood and brain extracellular fluid in the central nervous system. It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or hydrophilic molecules into the cerebral spinal fluid, while allowing the diffusion of small hydrophobic molecules (O₂, hormones, CO₂). The brain is as resistant to infection as it is because of the endothelial barrier. However, antibodies cannot pass through this barrier. Crucial hormones are “sent to” various sites where neurons sample the composition of the blood. Yet the blood-brain barrier generally blocks anything bigger than 500 Daltons; therefore, medications often cannot bypass it. This means that malignancies and conditions affecting brain function are incredibly difficult to treat.

Endothelial humoral response to mechanical stress is nothing short of astounding. It is noteworthy that dietary components and stresses can tip the balance of pro-coagulant/anti-coagulant to favor the former. The subsequent release of nitric oxide occurs intermittently in small amounts and can markedly orchestrate a cascade of inflammatory responses, which are often precursors to acute and chronic disease.

Our understanding of the complexities of endothelial functions and critical associations with their dysfunctions are the target of research that can have a significant impact on food design and food consumption patterns that promote better health.

References cited in this column are available from the authors.

Peter Pressman, M.D.,
Contributing Editor
CDR, Medical Corps, U.S. Navy, Director Expeditionary Medicine, Task Force for Business & Stability Operations
[email protected]

Roger Clemens, Dr.P.H.,
Contributing Editor
Chief Scientific Officer, ETHorn, La Mirada, Calif.
[email protected]