Nutrition Research

Summary

A common and early event in cardiovascular disease (CVD) happens when damage occurs to the vascular endothelium, the thin layer of cells that lines blood vessels. This damage impairs the function of the endothelium, a condition called endothelial dysfunction. Protecting the vascular endothelium helps minimize the risk of developing CVD and its manifestations, such as heart attack and stroke

The vascular endothelium is a major target for oxidative stress. Therefore, nutrients and dietary factors with antioxidant properties, in particular vitamin C, may protect the vascular endothelium from damage caused by oxidative stress. Additionally, vitamin C and certain flavonoids may increase the availability of nitric oxide, a compound that promotes vasodilation and assists endothelial function.

Condition Overview

The vascular endothelium refers to the inner lining of blood vessels. Although it is a simple, single layer of cells, the vascular endothelium is considered an active organ that responds to and secretes chemical signals.

The vascular endothelium regulates the passage of substances and cells from the blood to the tissues and is central to the regulation of vascular tone (the balance between blood vessel constriction and dilation).

Endothelial dysfunction is a term that refers to impaired functioning of the lining of blood vessels. It is characterized by:

  • impaired vasodilation
  • deficiency of nitric oxide
  • an "activated endothelium" that is in a state of inflammation, growth, and thrombosis (blood clotting)

Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. It is also a reversible disorder. As an early, reversible event in the development of cardiovascular disease (CVD), strategies to maintain and protect the endothelium are at the forefront of CVD preventive efforts. See below for specific information about nutrients and dietary factors relevant to endothelial dysfunction.

Additional reference

  • Hadi HA, et al. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vascular Health and Risk Management. 2005;1(3):183-98
DEFINITIONS
Vascular endothelium - the inner lining of blood vessels
Vasodilation - widening of a blood vessel
Vasoconstriction - narrowing of a blood vessel
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them
Reactive oxygen species (ROS) - highly unstable oxygen-containing compounds that react easily with nearby cellular structures, potentially causing damage
Antioxidant - a compound that prevents or repairs the damage caused by reactive oxygen species
Nitric oxide - a gaseous signalling molecule; in the vascular endothelium, nitric oxide promotes the relaxation of arterial walls, leading to vasodilation

Nutrition Research

DEFINITIONS
Test tube (in vitro) experiment - a research experiment performed in a test tube, culture dish, or other artificial environment outside of a living organism; in vitro is a Latin phrase meaning in glass
Animal experiment - a research experiment performed in a laboratory animal; many different animal species are studied in the laboratory, including terrestrial (land), aquatic (water), and microscopic animals
Observational study - a human research study in which no experimental intervention or treatment is applied, and participants are simply observed over time
Randomized controlled trial - a human research study in which participants are assigned by chance alone to receive either an experimental agent (the treatment group) or a placebo (the control group)
Placebo - a chemically inactive substance

 

Magnesium

What it does

General

  • Magnesium is an essential mineral that serves as a structural component of the skeleton; assists in hundreds of enzymatic reactions involved in the synthesis of energy, DNA, and proteins; and is required for proper nerve conduction and muscle contraction.

Endothelium-specific

  • Animal experiments indicate that severe magnesium deficiency (low concentration of magnesium in the blood) contributes to a pro-inflammatory state, thought to damage the endothelium and promote blood clotting in the arteries.
What we know
  • Low dietary intake of magnesium has been associated with higher levels of E-selectin, a protein indicative of inflammation in the endothelium.
  • Very high doses (700 to 1,200 milligrams/day) of oral magnesium may improve endothelial function in individuals with coronary heart disease.
  • The tolerable upper intake level (UL) for magnesium is 350 milligrams of supplemental magnesium per day. Because of the potential risks, especially in the presence of impaired kidney function, high-dose supplementation with magnesium should be conducted under medical supervision.

For references and more information, see the section on endothelial dysfunction in the Magnesium article.

Magnesium Flashcard. Main Functions: 1) Structural component of bones and teeth, 2) Regulates nerve transmission and muscle contraction, and 3) Assists in hundreds of essential cellular reactions. Good Sources: Whole Grains (wheat, oats, barley), brown rice, cooked, 1 cup = 86 mg; Green Leafy Vegetables (Swiss chard, spinach), spinach (boiled), 1 cup = 157 mg; Nuts (hazelnuts, cashews), almonds, 1 ounce or 23 almonds = 77 mg. Daily Recommendation: 400 mg for men 19-30 years, 420 mg for men 31 years and older; 310 mg for women 19-30 years, 320 mg for women 31 years and older. Special Notes: 1) Most people consume too little magnesium. 2) The Tolerable Upper Intake Level (UL) for magnesium is 350 mg/day from supplements. The UL does not apply to naturally occurring magnesium from food.

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Vitamin C

What it does

General

  • Vitamin C (ascorbic acid) is a water-soluble vitamin that neutralizes a variety of reactive oxygen species, recycles important cellular antioxidants, augments the functional activity of immune cells, and helps make collagen, L-carnitine, and several neurotransmitters.

Endothelium-specific

  • Oxidative stress is thought to be an early, causative event in the onset of endothelial dysfunction and atherosclerosis. The antioxidant activities of vitamin C may protect the vascular endothelium from damage caused by oxidative stress and increase the availability of nitric oxide, a potent vasodilator that is reduced in a dysfunctional endothelium.
What we know
  • Several randomized controlled trials have demonstrated that supplementation with vitamin C (500 milligrams/day) improves vasodilation in individuals with cardiovascular disease.
DEFINITIONS
Reactive oxygen species (ROS) - highly unstable oxygen-containing compounds that react easily with nearby cellular structures, potentially causing damage
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them
Antioxidants - compounds that prevent or repair the damage caused by reactive oxygen species
Vasodilator - an agent that promotes widening of a blood vessel

For references and more information, see the section on vasodilation in the Vitamin C article.

Vitamin C (ascorbic acid) Flashcard. Main Functions: 1) Antioxidant defense, 2) Enhances immune function, 3) Needed to make collagen, carnitine, and the neurotransmitters serotonin and norepinephrine. Good Sources: Fruit, 1 medium-sized kiwifruit = 90 mg; strawberries, 1 cup whole, 85 mg; Vegetables (broccoli, kale, tomatoes), sweet red pepper (one-half cup, chopped) = 95 mg. Daily Recommendation is 400 mg for all adults. Special Notes: 1) Heat destroys vitamin C. Try to eat fresh foods and cook by steaming, microwaving, or stir-frying. 2) Vitamin C in food is identical to vitamin C in supplements. 3) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 90 mg/day for men and 75 mg/day for women.

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Coenzyme Q10

What it does

General

  • Coenzyme Q10 is a compound that can be made inside the body and obtained from food and dietary supplements.
  • Coenzyme Q10 helps the body convert food into useable energy and functions as an antioxidant in cell membranes.

Endothelium-specific

  • The antioxidant properties of coenzyme Q10 may help reduce oxidative stress, thereby increasing the availability of nitric oxide, a potent vasodilator that is reduced in a dysfunctional endothelium.
  • Coenzyme Q10 may also reduce oxidation of low-density lipoprotein (LDL). Oxidized LDL readily accumulates at sites of endothelial injury and contributes to the development of atherosclerosis.
What we know
  • Combining the results from five, small, randomized controlled trials, supplemental coenzyme Q10 (150 to 300 milligrams/day for 4 to 12 weeks) modestly improved endothelial function in individuals with and without cardiovascular disease.
  • Although the results are promising, large, long-term trials are needed to confirm that coenzyme Q10 improves endothelial function. 
DEFINITIONS
Reactive oxygen species (ROS) - highly unstable oxygen-containing compounds that react easily with nearby cellular structures, potentially causing damage
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them
Antioxidants - compounds that prevent or repair the damage caused by reactive oxygen species
Vasodilator - an agent that promotes widening of a blood vessel

For references and more information, see the section on vascular endothelial function in the Coenzyme Q10 article.

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Flavonoids

What they do

General

  • Flavonoids are phytochemicals (chemicals produced by plants) that belong to a class of compounds called phenolics.
  • More than 5,000 varieties of flavonoids have been identified and hundreds of flavonoids can exist in a single food.
  • Many of the biological effects of flavonoids are related to their ability to modulate signalling pathways inside of cells.

Endothelium-specific

  • Inside endothelial cells, certain flavonoids may increase the production of nitric oxide, a potent vasodilator that is reduced in a dysfunctional endothelium.
What we know
  • Consuming flavonoid-rich foods and beverages has been associated with a reduced risk of coronary heart disease (CHD).
  • Several randomized controlled trials have demonstrated that consumption of certain flavonoid-rich beverages (black tea, purple grape juice, and high-flavanol cocoa powder) improves endothelial function in patients with CHD, elevated blood cholesterol, or type 2 diabetes.
DEFINITION
Vasodilator - an agent that promotes widening of a blood vessel

For references and more information, see the section on vascular endothelial function in the Flavonoids article.  

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Lipoic Acid

What it does

General

  • Lipoic acid (LA) is a compound that can be made inside the body and obtained from food and dietary supplements.
  • The primary function of LA is as a cofactor, or assistant, in several critical steps in energy metabolism. At high concentrations, LA functions as an antioxidant, binds metals, and facilitates glucose uptake and utilization.

Endothelium-specific

  • The antioxidant and metal-binding activities of LA may protect the vascular endothelium from damage caused by oxidative stress.
What we know
  • Only a few, small randomized controlled trials have tested the effect of LA on endothelial function in individuals with diabetes or metabolic syndrome. Intravenous infusion plus oral supplementation of LA improved endothelial function in these high-risk patient populations.
  • Research is needed to evaluate the effect of LA on endothelial function in healthy individuals.
DEFINITIONS
Antioxidants - compounds that prevent or repair the damage caused by reactive oxygen species
Reactive oxygen species (ROS) - highly unstable oxygen-containing compounds that react easily with nearby cellular structures, potentially causing damage
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them

For references and more information, see the section on vascular disease in the Lipoic Acid article.  

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Resveratrol

What it does

General

  • Resveratrol is a phytochemical (a chemical produced by plants) that belongs to a class of compounds called stilbenes.
  • Some plants produce resveratrol to protect themselves from UV radiation, infection, injury, and other forms of environmental stress.
  • Resveratrol is naturally found in peanuts, grapes, red wine, and some berries.

Endothelium-specific

  • Test tube experiments demonstrate that high concentrations of pure resveratrol inhibit platelet aggregation, enhance the production of nitric oxide (a gaseous molecule that relaxes arterial walls), and inhibit inflammatory enzymes.
What we know
  • In humans, orally ingested resveratrol is modified by the digestive tract, greatly reducing the dose and modifying the form of resveratrol that reaches the circulation.
  • Several small, randomized controlled trials have tested the effect of supplemental resveratrol on endothelial function and biomarkers of endothelial inflammation. These preliminary trials suggest that high-doses of supplemental resveratrol (>150 milligrams/day) may improve measures of endothelial function and inflammation.
  • However, the effect of resveratrol is temporary and there is currently no convincing evidence that these effects can be achieved by the amounts of resveratrol present in one to two glasses of red wine.
DEFINITION
Platelet aggregation - the clumping together of platelets, a type of blood cell; an early step in the formation of a blood clot
HIGHLIGHT
Supplemental resveratrol at doses greater than 1,000 milligrams (mg)/day might cause diarrhea or other gastrointestinal disturbances.

For references and more information, see the section on cardiovascular disease in the Resveratrol article

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Soy Isoflavones

What they do

General

  • Isoflavones are a type of phytochemical (a chemical produced by plants) that belong to a class of compounds known as phytoestrogens. Phytoestrogens have weak estrogenic activity, meaning that they might be able to either mimic or block the effects of estrogen inside certain body tissues.
  • Isoflavones are fermented by certain gut bacteria, and the resulting byproducts are thought to exert beneficial health effects.

Endothelium-specific

  • In test tube and animal experiments, isoflavones enhance the activity of antioxidant enzymes in endothelial cells and smooth muscle cells that make up arterial walls. An increase in antioxidant activity may protect the endothelium from damage caused by oxidative stress.
  • Additionally, isoflavones may increase the availability of nitric oxide, a potent vasodilator that is reduced in a dysfunctional endothelium.
What we know
  • In spite of the promising results from test tube and animal experiments, the majority of randomized controlled trials found no significant improvement in endothelial function following supplementation with isoflavone-containing soy products.
  • Isolated soy isoflavone supplements may have a very mild, beneficial effect on endothelial function in postmenopausal women, but the information is based on only a few, small trials. More research is needed to confirm that isoflavones improve endothelial function.
DEFINITIONS
Antioxidants - compounds that prevent or repair the damage caused by reactive oxygen species
Reactive oxygen species (ROS) - highly unstable oxygen-containing compounds that react easily with nearby cellular structures, potentially causing damage
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them
Vasodilator - an agent that promotes widening of a blood vessel

For references and more information, see the section on arterial function in the Soy Isoflavones article

Additional references

  • Siow RCM and Mann GE. Dietary isoflavones and vascular protection: Activation of cellular antioxidant defenses by SERMs or hormesis? Molecular Aspects of Medicine. 2010;31:468-77
  • Beavers DP, et al. Exposure to isoflavone-containing soy products and endothelial function: A Bayesian meta-analysis of randomised controlled trials. Nutrition Metabolism & Cardiovascular Diseases. 2012;22:182-91

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