Nutrition Research

Summary

Maintaining total-, low-density lipoprotein (LDL)-, and high-density lipoprotein (HDL)-cholesterol within healthy ranges is important for reducing atherosclerotic plaque formation and the risk of coronary heart disease (CHD). Several nutrients, dietary factors, food, and beverages have beneficial effects on blood cholesterol concentrations: omega-6 and omega-3 polyunsaturated fatty acids, fiber, phytosterols, and nuts all reduce total- and LDL-cholesterol; moderate consumption of alcoholic beverages increases HDL-cholesterol. There is also some evidence that supplemental garlic preparations reduce total- and LDL-cholesterol in individuals with abnormal blood cholesterol concentrations.

Condition Overview

Cholesterol is a type of lipid that is essential for health. It is required to make bile acids (necessary for the absorption of dietary fat and fat-soluble vitamins), steroid compounds (such as estrogen, androgen, and vitamin D), and cell membranes (which encase every cell in the body).

Cholesterol comes from two sources: it is made in the liver and obtained from the diet.

(1) Cholesterol Synthesis

The majority of cholesterol in the blood comes from the liver, which makes approximately 700 to 900 milligrams (mg) of cholesterol per day. In healthy individuals, the liver will lower the amount of cholesterol it makes in response to dietary intake.

(2) Dietary Cholesterol

We also obtain cholesterol from the food we eat. Cholesterol is found only in animal products, and the average dietary intake in the U.S. is approximately 250 to 300 mg per day. Rather than the amount of cholesterol consumed, however, the quality of dietary fat one eats has a major influence on the rate of cholesterol synthesis by the liver and the amount of cholesterol circulating in the blood. In general, high intake of saturated and trans fat raises LDL-cholesterol and lowers HDL-cholesterol concentrations.

Blood Cholesterol

Because blood (mostly water) and cholesterol (a type of lipid) do not mix, the body uses special carrier proteins to transport cholesterol through the bloodstream. These special carriers are called lipoproteins. Lipoproteins are spherical particles that pack cholesterol and other types of lipid on the inside while surrounded by water-friendly components on the outside.


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There are several types of lipoprotein particles that influence cardiovascular health:

(1) Low-Density Lipoprotein (LDL) carries cholesterol from the liver to all cells in the body. LDL-cholesterol (LDL-C) is referred to as “bad” cholesterol because it can contribute to atherosclerotic plaque formation. Circulating LDL particles are a target for oxidative damage, especially if they are small and dense. Once oxidized, LDL is more prone to being trapped inside arterial walls and contributing to plaque formation.

(2 & 3) Like LDL, Very-Low-Density Lipoprotein (VLDL) and Intermediate-Density Lipoprotein (IDL) are considered atherogenic lipoproteins. They travel in the bloodstream and deliver triglycerides (VLDL) and cholesterol (IDL) to tissues and cells throughout the body.

(4) High-Density Lipoprotein (HDL) carries cholesterol from the cells of the body back to the liver for recycling or disposal. HDL-cholesterol (HDL-C) is referred to as “good” cholesterol because it helps remove cholesterol from the arteries, reducing the formation of atherosclerotic plaque.

Maintaining total-, LDL-, VLDL-, and HDL-cholesterol within healthy ranges is important for reducing atherosclerotic plaque formation and the risk of developing coronary heart disease. A blood cholesterol profile will be interpreted in conjunction with other factors (such as family history, high blood pressure, smoking, type 2 diabetes, being overweight, and physical inactivity) in order to predict one’s 10-year risk for heart disease or stroke (http://www.cvriskcalculator.com/).  

See below for specific information about nutrients and dietary factors relevant to blood cholesterol concentration.

DEFINITIONS
Lipid - a large class of compounds that are insoluble in water; lipids include cholesterol, triglycerides, and fatty acids
Lipoprotein - a sphere-like particle that carries cholesterol and triglycerides through the bloodstream
Low-density lipoprotein (LDL) - a particle that carries cholesterol from the liver to all cells in the body
High-density lipoprotein (HDL) - a particle that carries cholesterol away from the cells in the body and to the liver for disposal
Lipoprotein (a) (Lp(a)) - a genetic variation of LDL; high blood levels of Lp(a) are associated with an increased risk of coronary heart disease and stroke
Oxidative damage- 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
Hyperlipidemia - too much lipid in the blood
Atherogenic - tending to promote the formation of plaque in the arteries

Commonly Used Medications

Statins

What they do
  • Statins are a class of cholesterol-lowering medications.
  • Statins interfere with the liver enzyme HMG-CoA reductase, which is required for cholesterol synthesis.
  • As a result of this interference, less cholesterol is produced by the liver, and less cholesterol ends up circulating in the blood.
What we know
  • Although there is some minor variability depending on the specific statin prescribed, statins can decrease LDL-C concentration by 20 to 40 percent.
  • Statins also significantly lower the risk of heart attack, ischemic stroke, and coronary revascularization procedures in both high-risk (previous evidence of vascular disease) and low-risk (no previous evidence of vascular disease) individuals.
  • As a class, adverse events associated with statin use are not common; however, myopathy (muscle pain or weakness) and increased risk of diabetes have been observed.

References

  • Goldstein JL & Brown MS. A Century of Cholesterol and Coronaries: From Plaques to Genes to Statins. Cell. 2015;161:161-72
  • Newman CB and Tobert JA. Statin Intolerance: Reconciling Clinical Trials and Clinical Experience. JAMA. 2015;313(10):1011-12
  • Cholesterol Treatment Trialists (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet. 2012;380(9841):581-90
  • Cholesterol Treatment Trialists (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. The Lancet. 2010;376:1670-81
  • Weng T.-C, et al. A systematic review and meta-analysis on the therapeutic equivalence of statins. Journal of Clinical Pharmacy and Therapeutics. 2010; 35:139-51

 

Table 1. Potential Interactions with Statins*
Supplements That May Increase Statin Side Effects Supplements That May Decrease Statin Activity
Niacin Antioxidant supplements (vitamin C, vitamin E, β-carotene, selenium)
  Grapefruit juice
  Phytosterols
*This list is not comprehensive. Talk to your doctor or pharmacist about potential interactions between any dietary supplements and medications you are taking.

For references and more information, see the Safety sections in the articles on vitamins, minerals, and dietary factors listed in Table 1.

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

 

Essential Fatty Acids

What they do

General

  • Essential fatty acids are a type of polyunsaturated fatty acid (PUFA). PUFAs have several double bonds in their structure that give them complex shapes and influence their function.
  • Essential fatty acids are structural components of every cell in the body, are converted to compounds that influence inflammation and immunity, and serve as an important source of energy.
  • There are two classes of essential fatty acids: omega-6 PUFA and omega-3 PUFA.

Cholesterol-specific

  • The long-chain omega-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), bind to cellular factors that influence the levels of lipoproteins in the bloodstream.
What we know
  • Omega-6 PUFA: The omega-6 PUFA, linoleic acid (LA), has been shown to be the most potent fatty acid for lowering serum total- and LDL-cholesterol (LDL-C).
  • Omega-3 PUFA: Although EPA and DHA supplementation reduces blood triglyceride concentration, EPA and DHA have different effects on LDL-C and HDL-cholesterol (HDL-C): DHA raises both LDL-C and HDL-C, whereas EPA has no significant effect on either one.
  • Overall, replacing dietary saturated fat with omega-6 and omega-3 PUFA from both plant and marine sources lowers LDL-C and reduces cardiovascular disease risk.
DEFINITION
Lipoproteins - sphere-like particles that carry cholesterol and triglycerides through the bloodstream

For references and more information, see the section about cardiovascular disease in the Essential Fatty Acids article.

There are two essential fatty acids: linoleic acid (an omega-6 polyunsaturated fatty acid) and alpha-linolenic acid (an omega-3 polyunsaturated fatty acid). These fatty acids are considered essential nutrients because they cannot be made in the body and must be consumed in the diet. Vegetable oils, especially safflower oil, sunflower oil, and corn oil, are a good source of linoleic acid.Flax and chia sees, walnuts, canola oil, and soybean oil are good sources of alpha-linoleic acid. Inside body tissues, the essential fatty acids are converted to long-chain fatty acids. Due to low efficiency of conversion, it is recommended to obtain eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) from additional sources. Oily fish, fish oil supplements, krill oil supplements, and algae oil supplements are good sources of EPA and DHA.

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Fiber

What it does

General

  • Fiber is a general term for carbohydrates that are resistant to digestion by human enzymes.
  • Fiber is considered an essential nutrient; it can be obtained from food, additives, and dietary supplements.
  • As fiber travels through the digestive tract, its physical properties (which vary depending on the type of fiber ingested) impart different health effects.
  • Beneficial health effects associated with fiber consumption include: satiety, gastrointestinal health, colonic health, and cardiovascular health.

Cholesterol-specific

  • Fiber may benefit cardiovascular health by decreasing serum cholesterol or by influencing blood glucose and the insulin response.
  • Additionally, fiber-rich foods may provide other nutrients, such as magnesium and potassium, that benefit the cardiovascular system by helping to reduce blood pressure.
What we know
  • Observational studies consistently find that high intakes of fiber-rich foods are associated with significant reductions in coronary heart disease risk and cardiovascular-related mortality.
  • Increased dietary intake and supplementation with viscous fibers in particular have been found to decrease total- and LDL-cholesterol concentrations. Oats, berries, legumes, nuts, and seeds are good sources of viscous fiber. 

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

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Niacin

What it does

General

  • Niacin (nicotinic acid) is a B-vitamin that assists hundreds of metabolic enzymes and helps convert food into usable energy.
  • Niacin supplements are available as nicotinamide or nicotinic acid.

Cholesterol-specific

  • The ways in which niacin lowers blood lipids (cholesterol and triglycerides) are still under investigation. Niacin participates in many cellular activities — the activation of receptors inside cells may be responsible for some of its lipid-lowering effects.
What we know
  • Pharmacological doses (greater than one gram per day) of niacin, but not nicotinamide, increase HDL-cholesterol levels while simultaneously decreasing LDL-cholesterol and triglycerides in individuals with abnormal blood lipids.
  • Because there are serious adverse side effects associated with high-dose niacin, niacin therapy should only be conducted under the supervision of a qualified health care provider.

For references and more information, see the section about high cholesterol and cardiovascular disease in the Niacin article.

SAFETY HIGHLIGHT

There are serious adverse side effects associated with high dose niacin supplements (>750 milligrams (mg) nicotinic acid/day)

  • Common side effects include flushing, itching, nausea, and vomiting.
  • Skin rashes, transient episodes of low blood pressure and headache, impaired glucose tolerance, infections, and elevated blood levels of uric acid have been reported.
  • Timed-release, high-dose niacin (≥500 mg/day) has resulted in liver cell damage.
  • Individuals should only undertake cholesterol-lowering therapy with niacin under the supervision of a qualified health care provider.

For references and more information, see the safety section in the Niacin article.

Niacin (vitamin B3) Flashcard. Main Functions: (1) helps convert food into useable energy, and (2) assists in DNA replication and repair. Good Sources. Niacin is found in many foods; yeast, meat, cereal, and legumes are especially good sources of niacin. Meat (beef, fish, poultry), chicken (light-meat), 3 ounces, 7.3-11.7 mg. Legumes (beans, peas, lentils), peanuts, 1 ounce (35 peanuts), 3.8 mg; Cereal (fortified), 1 cup, 20-27 mg. Daily Recommendation. 16 mg NE for men, 14 mg NE for women, NE=niacin equivalents, 1 NE=1 mg niacin=60 mg tryptophan. Special Notes. (1) The amino acid tryptophan can be converted to niacin inside the body. (2) Supplemental niacin can cause side effects, such as flushing, itching, nausea, and vomiting; the Tolerable Upper Intake Level (UL) is 35 mg/day. 

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Pantothenic Acid (Vitamin B5)

What it does

General

  • Pantothenic acid is a B-vitamin that helps convert food into usable energy and assists in the synthesis of fat, cholesterol, steroid hormones, neurotransmitters, and hemoglobin.

Cholesterol-specific

  • Pantothenic acid itself is not effective in lowering blood cholesterol, but a derivative of pantothenic acid, pantethine, is under investigation for its cholesterol-lowering effects in diabetic individuals.
  • It is not yet known how pantethine lowers blood lipids, but it may inhibit cholesterol synthesis or improve triglyceride and LDL-cholesterol (LDL-C) breakdown in the liver.
What we know
  • Some human studies demonstrate that pantethine effectively lowers total-cholesterol, LDL-C, and triglyceride levels, and raises HDL-cholesterol in diabetic individuals with abnormal blood lipids.
  • The decision to use pantethine should only be made in collaboration with a qualified health care provider.

For references and more information, see the section about pantethine and high cholesterol in the Pantothenic Acid article

Pantothenic Acid Flashcard. Main Functions: (1) helps convert food into useable energy; (2) helps make and break down fats; (3) helps make cholesterol, steriod hormones, neurotransmitters, and hemoglobin; and (4) helps the liver break down certain drugs and toxins. Good Sources: Dairy products (milk, yogurt, cheese), plain nonfat yogurt, 8 ounces, 1.6 mg; meat (organ metas, beef, fish), trout (3 ounces; about the size of a deck of cards), 1.9 mg; sunflower seeds, 1 ounce, 2.0 mg. Daily Recommendation: 5 mg for all adults. Special Notes: (1) Pantothenic acid is widespread in the food supply, and dietary deficiency is rare. (2) Little or no toxicity has been associated with supplemental pantothenic acid.

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Phytosterols

What they do
  • Phytosterols are a group of plant-derived compounds that are similar in structure to cholesterol.
  • The two types of phytosterols are called plant sterols and plant stanols.
  • Dietary sources of phytosterols include unrefined vegetable oils, whole grains, nuts, and legumes; enriched spreads are also a source of phytosterols.

Cholesterol-specific

  • Phytosterols inhibit the absorption of dietary cholesterol.
What we know
  • Several randomized controlled trials have found that daily consumption of products enriched with plant sterols or plant stanols significantly lowers serum total- and LDL-cholesterol (LDL-C) concentrations.
  • Approximately two grams of phytosterols per day reduce serum LDL-C by approximately 9 to 14 percent.

For references and more information, see the section on LDL cholesterol in the Phytosterols article

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Soy Isoflavones

What they do
  • 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.

Cholesterol-specific

  • Estrogen has a well-established beneficial effect on blood lipids; thus, the potential for isoflavones to mimic some estrogenic activities may favorably affect blood cholesterol concentrations.
What we know
  • Substitution of soy protein (rich in isoflavones and many other bioactive substances) for animal protein modestly reduces LDL-cholesterol by approximately 4 to 6 percent. However, it does not appear that soy isoflavones themselves are responsible for the observed cholesterol-lowering effect of soy protein.
  • Overall, isolated soy isoflavone supplements do not appear to have favorable effects on blood lipid profiles.

For references and more information, see the section on cholesterol in the Soy Isoflavones article.

Additional references

  • Tikkanen MJ. Estrogens, Progestins, and Lipid Metabolism. Maturitas. 1996;23Suppl:S51-S55
  • Messina M. Soy foods, isoflavones, and the health of postmenopausal women. American Journal of Clinical Nutrition. 2014;100(suppl):423S-430S

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Alcoholic Beverages

What they do

General

  • Alcoholic beverages contain ethanol and other ingredients with bioactive properties that may affect health.
  • When consumed in moderation (no more than two drinks/day for men and one drink/day for women), alcoholic beverages have been associated with beneficial effects in the cardiovascular system.

Cholesterol-specific

  • The way in which alcohol influences blood cholesterol is not fully understood. Alcohol may increase the production of a protein in liver cells that promotes transport of HDL from the liver into the bloodstream. HDL then collects cholesterol from the body and returns it to the liver for recycling or disposal.
What we know
  • Short-term randomized controlled trials have consistently demonstrated that moderate daily alcohol ingestion significantly increases HDL-cholesterol (HDL-C) levels.
  • It has been estimated that HDL-C concentrations increase by approximately 1.862 milligrams/deciliter (mg/dL) per standard alcoholic drink.

For references and more information, see the section on Potential Health Benefits of Moderate Alcohol Consumption in the Alcoholic Beverages article.

Additional reference

  • De Oliveira ER, et al., Alcohol Consumption Raises HDL Cholesterol Levels by Increasing the Transport Rate of Apolipoproteins A-I and A-II. Circulation. 2000;102:2347-52

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Coffee

What it does

General

  • Coffee is a complex mixture of chemicals. In addition to caffeine, coffee contains several phytochemicals that can influence human health.

Cholesterol-specific

  • Two phytochemicals in coffee beans, cafestol and kahweol, can raise serum total and LDL-cholesterol concentrations.
  • Cafestol and kahweol are removed from coffee by paper filters, thus boiled and french press coffee contain relatively high levels of cafestol and kahweol compared to filtered coffee.
What we know
  • Randomized controlled trials have confirmed the cholesterol-raising effect of unfiltered, boiled coffee.
  • A pooled analysis of randomized controlled trials reported that, on average, drinking six cups or more per day of unfiltered coffee significantly raised total-cholesterol (8.1 mg/dL), LDL-cholesterol (5.4 mg/dL), and triglyceride (12.6 mg/dL) concentrations.
  • Although unfiltered coffee consumption increases blood cholesterol concentrations, there appears to be no significant association between moderate coffee consumption (three to four cups per day) and the risk of coronary heart disease.

For references and more information, see the section on LDL cholesterol in the Coffee article.

Additional reference

  • Eilat-Adar S, et al., Nutritional Recommendations for Cardiovascular Disease Prevention. Nutrients. 2013;5:3646-83

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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.
  • Organosulfur compounds and their breakdown products may be responsible for some beneficial health effects of garlic.

Cholesterol-specific

  • In test tube and animal experiments, supplemental garlic preparations inhibit enzymes involved in the synthesis of cholesterol and reduce the absorption of cholesterol in the intestine.
What we know
  • Many randomized controlled trials have examined the effects of supplementation with various garlic preparations on serum lipid profiles in individuals with elevated and normal serum cholesterol levels.
  • Overall, supplemental garlic, taken for at least two months, has a beneficial effect on total-cholesterol and LDL-cholesterol levels in individuals with elevated total-cholesterol.
  • All garlic preparations are highly tolerable and associated with only minor side effects, such as garlic odor or gastrointestinal symptoms.

For references and more information, see the section on lipid profiles in the Garlic article

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Nuts

What they do
  • Nuts are a good source of soluble fiber, phytosterols, mono- and polyunsaturated fatty acids, protein, certain vitamins (folate, vitamin E), and minerals (calcium, magnesium, potassium).
  • Examples of tree nuts include: almonds, Brazil nuts, cashews, hazelnuts, macadamia nuts, pecans, pistachios, and walnuts.
  • Peanuts are not nuts; they are legumes. However, peanuts are nutritionally similar to tree nuts and have some of the same beneficial properties.

Cholesterol-specific

  • The soluble fiber and phytosterols present in nuts and peanuts inhibit intestinal absorption of dietary cholesterol, which can lead to reductions in serum total- and LDL-cholesterol (LDL-C).
  • Additionally, substituting dietary saturated fat with unsaturated fat (abundant in nuts and peanuts) lowers LDL-C concentration.
What we know
  • Regular nut consumption (one ounce at least five times per week) is associated with a significantly lower risk of coronary heart disease.
  • Numerous randomized controlled trials demonstrate that adding nuts (one to two ounces daily) to a diet that is low in saturated fat results in significant reductions in serum total- and LDL-cholesterol concentrations in people with normal or elevated serum cholesterol.
HIGHLIGHT
  • Nuts are packed with healthy fats and, therefore, calories.
  • One ounce of nuts contains approximately 160 calories and 14 to 19 grams of fat (mainly mono- and polyunsaturated fatty acids).
  • One ounce of nuts equals approximately: 24 almonds, 8 medium Brazil nuts*, 18 medium cashews, 12 hazelnuts, 12 macadamia nuts, 15 pecan halves, 47 pistachios, 14 walnut halves, and 35 peanuts.
  • It is recommended to substitute nuts for sources of saturated fat.

*Depending on growth conditions, a single Brazil nut could contain exceedingly high levels of selenium. 

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

Additional reference

  • Dreher ML and Maher CV. The Traditional and Emerging Role of Nuts in Healthful Diets. Nutrition Reviews. 1996;54(8):241-5

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