Nutrition Research

picture of a normal artery with normal blood flow and an artery containing plaque buildup

Summary

Atherosclerosis, the buildup of plaque inside arterial walls, is an early event in the development of cardiovascular disease (CVD). There is very limited evidence that nutrients influence the progression of atherosclerosis. Most research indicates that nutrients with antioxidant properties influence endothelial dysfunction, a condition that precedes atherosclerosis. There is also evidence that some nutrients and phytochemicals reduce blood pressure and serum lipid levels, conditions that increase the risk of developing atherosclerosis.

Disease Overview

Atherosclerosis is a disease in which plaque builds up inside arterial walls. The formation of atherosclerotic plaque is an early event in the development of coronary heart disease (CHD) and progresses slowly over many years.

The process begins with endothelial dysfunction, mainly in medium- and large-sized arteries. At sites of endothelial dysfunction, damage to arterial walls may occur more quickly than repair. As a result, blood clotting proteins, immune cells, fat, and cholesterol accumulate at the site of damage, forming what is known as plaque. 

Over time, plaque can:

  • narrow the opening of an artery, thereby reducing blood flow
  • decrease elasticity
  • become unstable and rupture, thereby creating blood clots or pieces of plaque that enter the bloodstream

Ultimately, blood clots or pieces of plaque may become lodged in an artery, causing a heart attack or stroke. Because atherosclerosis develops slowly over many years, there are several opportunities to intervene and slow its progression.

See below for specific information about nutrients and dietary factors relevant to atherosclerosis.

Conditions Caused by Narrowed or Blocked Arteries

Peripheral arterial disease (PAD) - atherosclerosis in the arteries to the head, organs, arms and legs
Coronary artery disease (CAD) - atherosclerosis in the arteries that supply blood to the heart
Carotid artery disease - atherosclerosis in the arteries that supply blood to the brain

DEFINTIONS
Artery (adjective: arterial) - a muscular-walled blood vessel that carries blood away from the heart
Plaque - a deposit of fat, cholesterol, immune cells, fibrin (a blood clotting protein), and other substances that forms inside arterial walls

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)

 

Copper

What it does

General

  • Copper is an essential trace mineral that assists in energy production, iron utilization, antioxidant defense, and the synthesis of neurotransmitters and connective tissue.

Atherosclerosis-specific

  • Both copper excess and copper deficiency have been implicated in the development of atherosclerosis.
  • In test tube experiments, free copper promotes the oxidation of low-density lipoprotein (LDL), which makes it more atherogenic.
  • On the other hand, copper deficiency could impair the activity of several copper-containing antioxidant enzymes, suggesting that copper deficiency, as well as excess, could increase the risk of atherosclerosis.
What we know
  • Several observational studies have found that increased copper concentration in the blood is associated with an increased risk of cardiovascular disease (CVD).
  • However, it is important to note that over 90% of copper is carried inside ceruloplasmin, a copper storage protein in the blood. Ceruloplasmin fluctuates under certain conditions of physical stress, such as trauma, inflammation, and disease. Therefore, elevated copper concentration in the blood may simply be indicative of the inflammation that accompanies atherosclerosis.
  • Several randomized controlled trials of copper supplementation demonstrate that high intake of copper (6 milligrams/day for six weeks) does not increase oxidative stress or promote LDL oxidation in the human body.
  • The role of copper in the development of atherosclerosis remains unclear. More research is needed to determine if copper imbalance, either too high or too low, influences the risk of CVD.

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

Copper Flashcard. Main Functions: 1) frees iron from storage so it can be used to make red blood cells, 2) assists antioxidant enzymes, and 3) assists in the formation and maintenance of connective tissue. Good Sources: shellfish (oysters, clams, crab), oysters, 6 medium = 2,397 micrograms; nuts (hazelnuts, almonds), cashew nuts, raw, 1 ounce or 18 cashews = 622 micograms; legumes (beans, peas, lentils), lentils (cooked), 1 cup=497 micrograms; Daily Recommendation: 900 micrograms for all adults; Special Notes: 1) Liver (from lamb, veal, beef, and geese) is also a rich source of copper. 2) Copper is widely distributed in food; a varied diet should provide enough copper to meet the daily recommendation. 3) Copper toxicity is rare. The Tolerable Upper Intake Level (UL) for adults is 10,000 micrograms/day from food and supplements.

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Vitamin K

What it does

General

  • Vitamin K is a fat-soluble vitamin that assists in blood clotting and modifies certain proteins to a calcium-binding form.
  • Naturally occurring vitamin K includes a number of different vitamin K compounds, classified as either vitamin K1 (phylloquinone) or vitamin K2 (menaquinones).

Atherosclerosis-specific

  • Vitamin K-modified proteins facilitate calcification of bone yet prevent calcification of soft tissues like cartilage and blood vessels.
  • Insufficient dietary vitamin K impairs the modification of these proteins, potentially increasing the risk of arterial calcification.
What we know
  • Overall, observational studies have not found an association between vitamin K1 intake and arterial calcification.
  • Only one small randomized controlled trial demonstrated that supplementation with vitamin K1 modestly reduced the progression of coronary artery calcification in older (60 to 80 years of age) men and women.
  • Research in humans is very limited and more studies are needed to determine if and how vitamin K1 supplementation might influence arterial calcification.
DEFINITIONS
Calcification - the deposition of calcium salts in tissues
Arterial calcification - an active, organized, highly complex process, similar to normal bone formation, in which calcium salts are deposited at sites of atherosclerotic plaque rupture
HIGHLIGHT
  • It is not known what causes certain vascular smooth muscle cells inside arterial walls to begin the process of arterial calcification. In fact, not all atherosclerotic plaques become calcified.
  • When it does occur, calcification is the response to, not the cause of, disease progression and plaque rupture.
  • Calcium intake (from diet and supplements) is not associated with increased coronary artery calcification.

References

  • Frink RJ. Inflammatory Atherosclerosis: characteristics of the injurious agent. Sacramento (CA): Heart Research Foundation; 2002. Available from: http://www.ncbi.nlm.nih.gov/books/NBK2025
  • Kopecky SL and Singer AJ. Calcium Supplementation: Does Protecting Against Fracture Risk Increase the Risk of Cardiovascular Diseases? [webinar] National Osteoporosis Foundation, August 17, 2015
  • Samelson EJ, et al. Calcium intake is not associated with increased coronary artery calcification: the Framingham Study. AJCN 2012;96:1274-80

For references and more information, see the section on vascular calcification in the Vitamin K article.

Vitamin K Flashcard. Main Functions: 1) Assists in blood clotting, 2) promotes bone calcification, and 3) Prevents blood vessel calcification. Good Sources: There are two forms of naturally occurring vitmain K: vitmain K1 (phylloquinone) and vitmain K2 (menaquinones). Vitamin K1 sources include green leafy vegetables and plant oils, kale (raw, chopped), 1 cup=472 micrograms; canola oil, 1 tablespoon=10 micrograms; Vitamin K2 sources are fermented food and gut bacteria: there is no dietary requiremetn for vitamin K2 at this time.

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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 to useable energy and functions as an antioxidant in cell membranes.

Atherosclerosis-specific

  • The antioxidant properties of coenzyme Q10 may help reduce oxidative stress, protect cell membranes in arterial walls, and prevent the oxidation of lipoproteins (which makes them more atherogenic).
What we know
  • In test tube experiments, coenzyme Q10 inhibits the oxidation of low-density lipoprotein (LDL); oxidized LDL represents an early contributor to the development of atherosclerosis.
  • In animal studies, very high doses of coenzyme Q10 alone and in combination with vitamin E inhibits the formation of atherosclerotic lesions.
  • In spite of the promising results from test tube and animal experiments, research is needed to determine whether coenzyme Q10 supplementation can inhibit the development or progression of atherosclerosis in humans.
DEFINITIONS
Antioxidant - a compound that prevents or repairs 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
Lipoprotein - a sphere-like particle that carries cholesterol and triglycerides through the bloodstream

For references and more information, see the section on cardiovascular disease in the Coenzyme Q10 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 mitochondrial energy metabolism. At high concentrations, LA functions as an antioxidant, binds metals, and facilitates glucose uptake and utilization.

Atherosclerosis-specific

  • The antioxidant and metal-binding activities of LA may be particularly beneficial for diseases affected by oxidative stress, such as atherosclerosis.
What we know
  • Test tube experiments indicate that by binding iron and copper, LA interferes with the recruitment of immune cells to sites of injury on blood vessel walls, a crucial initiating event in atherosclerosis. 
  • Test tube experiments also indicate that LA can inhibit the movement of a protein (called NFκB) that plays a central role in inflammation and the development of atherosclerosis.
  • No research has been conducted in humans. Therefore, in spite of the results from test tube experiments, research is needed to determine whether LA supplementation can inhibit the development or progression of atherosclerosis in humans.
DEFINITIONS
Antioxidant - a compound that prevents or repairs 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 Biological Activities 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.

Atherosclerosis-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 metabolized by the digestive tract, greatly reducing the dose and modifying the form of resveratrol that reaches the circulation.
  • There is no convincing evidence that resveratrol has cardioprotective effects in humans, particularly in the amounts present in one to two glasses of wine.

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

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Garlic

What it does

General

  • Garlic is a rich source of organosulfur compounds, a category of phytochemicals that give garlic its pungent smell and taste.
  • These organosulfur compounds and their breakdown products may be responsible for some beneficial health effects of garlic.

Atherosclerosis-specific

  • Test tube experiments indicate that organosulfur compounds in garlic can inhibit the growth and migration of vascular smooth muscle cells, a feature of advanced atherosclerotic lesions.
  • Supplemental garlic may reduce the risk of atherosclerosis through its mild, beneficial effects on serum lipids, platelet aggregation, and blood pressure.
What we know
  • Evidence from one randomized controlled trial indicates that dehydrated garlic (900 milligrams/day for four years) reduced the rate of atherosclerotic plaque progression only in women.
  • Because research in humans is very limited, more studies are needed to determine if garlic preparations significantly influence the progression of atherosclerotic plaque.

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

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