Nutrition Research

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.

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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 and recycles important cellular antioxidants.
• Vitamin C is also a cofactor in numerous enzymatic reactions involved in the making of collagen, L-carnitine, and several neurotransmitters, and in the regulation of gene expression.

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

• A pooled analysis of randomized controlled trials found that supplementation with vitamin C improved markers of endothelial function, but the benefits were only seen in older individuals (>56 years).

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

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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.

For references and more information, see the section on vascular endothelial dysfunction 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.

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.

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.

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.

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 randomized controlled trials. Nutrition Metabolism & Cardiovascular Diseases. 2012;22:182-91

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Authors and Reviewers

Written in May 2015 by:
Giana Angelo, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in September 2015 by:
John F. Keaney, Jr., M.D.
Medical Director, Heart and Vascular Center of Excellence
Chief, Division of Cardiovascular Medicine
University of Massachusetts Medical School and Memorial Medical Center
Mary C. DeFeudis Professor of Biomedical Research
University of Massachusetts Medical School

Copyright 2015-2025 Linus Pauling Institute

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