What if I told you that your body has an internal medicine chest the size of a football field that is packed full of phenomenal and powerful remedies for inflammation, poor blood flow, high blood pressure, memory loss and virtually every other condition imaginable? Would you believe it? Well, it is true. This medicine chest is the lining of cells along the interior surface of all blood vessels. The technical term for this tissue is the endothelium and the cells that form this lining are called endothelial cells. From the heart to the smallest capillary all vascular tissue has an endothelium. If all of the endothelial cells in the body were laid out flat, the endothelial surface area would be about the size of a football field. That is incredible to think about isn’t it? Even more incredible is the way that nutrition and dietary supplements can impact the endothelium.

The Important Functions of the Endothelium

Here is a brief look at some of the important and profound functions that the endothelium is responsible for:

  • Barrier function—the endothelium acts as a semi-selective barrier controlling the passage of materials and the transit of white blood cells into and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelial layer are associated with inflammation and swelling.
  • Inflammation—the endothelium helps to control inflammation in order to protect the deeper layers of blood vessels.
  • Blood clotting (thrombosis & fibrinolysis)—the surface of the endothelium normally possesses factors that prevent the formation of blood clots. When it lacks these protective factors in can lead to the formation of blood clots that could lead to the build up of plaque or the formation of a large clot that may break off and cause a heart attack or stroke.
  • The constriction and dilation of blood vessels—hence, the endothelium plays a key role in controlling blood flow and blood pressure.
  • In some organs, there are highly differentiated endothelial cells to perform specialized “filtering” functions. Examples of such unique endothelial structures include those found in the kidneys (the renal glomerulus) and those that protect the brain (the blood–brain barrier).

The loss of proper endothelial function is a hallmark for vascular diseases, and is often regarded as a key early event in the development of atherosclerosis (hardening of the arteries). Impaired endothelial function is often seen in patients with diabetes, hypertension, high cholesterol levels, as well as in smokers.

The main causes of endothelial dysfunction are high blood sugar levels and damage caused by free radicals and pro-oxidants. One of the key consequences of this damage is a diminished ability to manufacture nitric oxide, a key chemical messenger used by the endothelial cells used to perform its duties.

The Role of Nutrition and Endothelial Function

The amazing thing about this barrier is that it is only one cell thick. It is kind of like shingles on a roof. If this barrier is damaged, it really sets in motion all of the factors that ultimately lead to the formation of the arterial plaque that is the hallmark feature of atherosclerosis (hardening of the arteries). The endothelial cells can be damaged by free radicals and pro-oxidants as well as by immune, viral, chemical and various drugs. Therefore, it is absolutely critical to support healthy endothelial function. Virtually all of the compounds that you have ever heard of that provides benefits to the vascular system, whether it is dark chocolate, pomegranate, olive oil, nuts and seeds, grape seed extract, arginine, coenzyme Q10 or fish oil, all impact endothelial function. One of the key benefits of the heart healthy Mediterranean diet is that it greatly improves endothelial function.

Many nutrients have important benefits to the cardiovascular system based upon their role in the function of the endothelium and heart cells. A deficiency of any essential nutrient can have deleterious effects of cardiovascular structure or function. Taking a multiple vitamin and mineral formula that provides at the recommended dietary intake (RDI) is important nutritional insurance. The other recommended foundational supplements of fish oils and a procyanidin extract like grape seed or pine bark are also important. The benefits of the longer-chain omega-3 fatty acids EPA, DHA, and DPA for cardiovascular health has been demonstrated in more than 300 clinical trials. Supplementation with these omega-3 fatty acids exert many benefits to both the heart and blood vessels.  For general support of heart health, the dosage recommendation is 1,000 mg EPA+DHA+DPA per day. In those needing more support the dosage is up to 3 g per day.

The Power of Procyanidins

One of the keys to eating a diet high in antioxidant activity is focusing on flavonoids, a type of plant pigment and a member of the larger polyphenol family. As a class of compounds, flavonoids are often called “nature’s biological response modifiers” because of their anti-inflammatory, anti-allergic, antiviral and anticancer properties. Many of the super foods like cacao, acai, goji, blueberries, etc., owe their benefits to their flavonoid content. While different flavonoids have different effects in the body, the key factor may not be a high intake of any one particular flavonoid, but rather a high total flavonoid intake that also provides a high variety of flavonoids rather than any one particular flavonoid class. There are more than 8,000 different types of flavonoids out there in nature.

What the research also shows is that it does not seem to matter where the flavonoids come from, e.g., through dietary sources such as legumes, fruit, green tea, coffee, chocolate or through flavonoid-rich extracts (grape seed, ginkgo, milk thistle, pine bark, bilberry, etc.), as long as an effective dosage is being taken. The caveat is that the proanthocyanidin flavonoids must be a major part of the flavonoid intake. Good dietary sources of these compounds are found in red or black grapes (especially the seeds), apples, cacao, cocoa, dark chocolate, berries (especially blueberries, cranberries, and black currants), certain nuts (e.g., hazelnuts, pecans, and pistachios) and red wine. So, with this caveat on the importance of proanthocyanidins in mind, what is an effective dosage of flavonoids? The best evidence on determining an effective dosage of total flavonoid intake is clinical trials with either well-defined sources of flavonoids from food and beverages, or from flavonoid-rich extracts. Fortunately, there has been an explosion of good scientific studies on a wide variety of flavonoid sources. For example, there are fantastic studies with proanthocyanidin-rich extracts from grape seed, cocoa, pomegranate, and pine bark, as well as flavonoid rich extracts from citrus, soy, and green tea extract all showing significant clinical benefits including in the following health conditions:

• Asthma
• Atherosclerosis (hardening of the arteries)
• Attention deficit disorder
• High blood pressure
• High cholesterol levels
• Male infertility
• Mild cognitive impairment
• Menopausal symptoms
• Osteoarthritis
• Periodontal disease
• Varicose veins, venous insufficiency and capillary fragility
• Visual function, retinopathy and macular degeneration

There have also been a large number of studies with flavonoid-rich sources looking at more immediate effects, such as their effect on blood vessel function, blood flow, or antioxidant capacity. Most of the studies with the aforementioned flavonoid-rich extracts have used an average dosage of about 300 mg per day to show an effect. Longer-term studies show even more benefit. For example, one of the best examples of the practical effect seen by normalizing endothelial function is with grape seed extract (standardized to contain 95 percent procyanidolic oligomers) in people with high blood pressure. There are now three very well designed double-blind clinical trials that show that within the first month of supplementation with 300 mg of grape seed extract it is able to normalize high blood pressure in most patients with pre-hypertension to moderate high blood pressure.1-3 Similar studies exist with pine bark (Pycnogenol), pomegranate, hibiscus and hawthorn extracts—all natural products rich in procyanidins.4 And, all used a dosage close to 300 mg per day to see a clinical effect.

Takeaway Message

Here is the key point of the article: Our vascular health is largely determined by the health, integrity, and function of the endothelium. Nutrition plays a key role in protecting and enhancing endothelial cells. A variety of flavonoid-rich extracts have shown a multitude of health benefits many of which relate directly to improved endothelial cell function. Of particular importance are procyanidin-rich extracts like grape seed, cocoa, pomegranate and pine bark.


  1. Schön C, Allegrini P, Engelhart-Jentzsch K, Riva A, Petrangolini G. Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers. Nutrients. 2021 Feb 17;13(2):654.
  2. Odai T, Terauchi M, Kato K, Hirose A, Miyasaka N. Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2019 Nov 20;11(12):2844.
  3. Terauchi M, Horiguchi N, Kajiyama A, et al. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. Menopause. 2014 Sep;21(9):990-6.
  4. Ren J, An J, Chen M, Yang H, Ma Y. Effect of proanthocyanidins on blood pressure: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2021 Mar;165:105329. 

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