Folic Acid & Cardiovascular Disease

Cardiovascular disease involves any disorder of the heart and blood vessels that make up the cardiovascular system. Coronary heart disease occurs when blood vessels which supply the heart become clogged or blocked, increasing the risk of a heart attack. Vascular damage can also occur to blood vessels supplying the brain, and can result in a stroke.

Cardiovascular disease is the most common cause of death in industrialized countries such as the US, and is on the rise in developing countries. The National Heart, Lung, and Blood Institute of the National Institute of Health has identified many risk factors for cardiovascular disease, including an elevated LDL-cholesterol level, high blood pressure, a low HDL-cholesterol level, obesity, and diabetes1 In recent years, researchers have identified another risk factor for cardiovascular disease, an elevated homocysteine level. Homocysteine is an amino acid normally found in blood, but elevated levels have been linked with coronary heart disease and stroke.234567891011121314 Elevated homocysteine levels may impair endothelial vasomotor function, which determines how easily blood flows through blood vessels.15 High levels of homocysteine also may damage coronary arteries and make it easier for blood clotting cells called platelets to clump together and form a clot, which may lead to a heart attack.16

A deficiency of folate, vitamin B12 or vitamin B6 may increase blood levels of homocysteine, and folate supplementation has been shown to decrease homocysteine levels and to improve endothelial function.171819 At least one study has linked low dietary folate intake with an increased risk of coronary events.20 The folic acid fortification program in the U. S. has decreased the prevalence of low levels of folate and high levels of homocysteine in the blood in middle-aged and older adults.21 Daily consumption of folic-acid fortified breakfast cereal and the use of folic acid supplements has been shown to be an effective strategy for reducing homocysteine concentrations.22

Evidence supports a role for supplemental folic acid for lowering homocysteine levels, however this does not mean that folic acid supplements will decrease the risk of cardiovascular disease. Clinical intervention trials are underway to determine whether supplementation with folic acid, vitamin B12, and vitamin B6 can lower risk of coronary heart disease. It is premature to recommend folic acid supplementation for the prevention of heart disease until results of ongoing randomized, controlled clinical trials positively link increased folic acid intake with decreased homocysteine levels AND decreased risk of cardiovascular disease.

Folic Acid & Cancer

Some evidence associates low blood levels of folate with a greater risk of cancer.23 Folate is involved in the synthesis, repair, and function of DNA, our genetic map, and there is some evidence that a deficiency of folate can cause damage to DNA that may lead to cancer.24 Several studies have associated diets low in folate with increased risk of breast, pancreatic, and colon cancer.2526 Over 88,000 women enrolled in the Nurses' Health Study who were free of cancer in 1980 were followed from 1980 through 1994. Researchers found that women ages 55 to 69 years in this study who took multivitamins containing folic acid for more than 15 years had a markedly lower risk of developing colon cancer.27 Findings from over 14,000 subjects followed for 20 years suggest that men who do not consume alcohol and whose diets provide the recommended intake of folate are less likely to develop colon cancer.28 However, associations between diet and disease do not indicate a direct cause. Researchers are continuing to investigate whether enhanced folate intake from foods or folic acid supplements may reduce the risk of cancer. Until results from such clinical trials are available, folic acid supplements should not be recommended to reduce the risk of cancer.

Folic Acid & Methotrexate for Cancer

Folate is important for cells and tissues that rapidly divide.29 Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. Methotrexate is a drug often used to treat cancer because it limits the activity of enzymes that need folate.

Unfortunately, methotrexate can be toxic, producing side effects such as inflammation in the digestive tract that may make it difficult to eat normally.303132 Leucovorin is a form of folate that can help "rescue" or reverse the toxic effects of methotrexate.33 There are many studies underway to determine if folic acid supplements can help control the side effects of methotrexate without decreasing its effectiveness in chemotherapy.3435 It is important for anyone receiving methotrexate to follow a medical doctor's advice on the use of folic acid supplements.

Folic Acid & Methotrexate for Non-Cancerous Diseases

Low dose methotrexate is used to treat a wide variety of non-cancerous diseases such as rheumatoid arthritis, lupus, psoriasis, asthma, sarcoidosis, primary biliary cirrhosis, and inflammatory bowel disease.36 Low doses of methotrexate can deplete folate stores and cause side effects that are similar to folate deficiency. Both high folate diets and supplemental folic acid may help reduce the toxic side effects of low dose methotrexate without decreasing its effectiveness.3738 Anyone taking low dose methotrexate for the health problems listed above should consult with a physician about the need for a folic acid supplement.

Related Links: What is folate? | What are some important links between folate and my health? | What foods provide folate? | How much folate do I need? | What happens if I do not get enough folate? | Do I need extra folate? | Can folate be harmful? | What are some of the current issues and controversies about folate? | Does folate interact with any medicines or supplements?

Disclaimer

Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate. However, this information is not intended to constitute an "authoritative statement" under Food and Drug Administration rules and regulations.

About Source: ODS

The mission of the Office of Dietary Supplements (ODS) is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public to foster an enhanced quality of life and health for the U.S. population.

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Health professionals and consumers need credible information to make thoughtful decisions about eating a healthful diet and using vitamin and mineral supplements. These Fact Sheets provide responsible information about the role of vitamins and minerals in health and disease. Each Fact Sheet in this series received extensive review by recognized experts from the academic and research communities.

The information is not intended to be a substitute for professional medical advice. It is important to seek the advice of a physician about any medical condition or symptom. It is also important to seek the advice of a physician, registered dietitian, pharmacist, or other qualified health professional about the appropriateness of taking dietary supplements and their potential interactions with medications.

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Footnotes

  1. Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health, September 2002. NIH Publication No. 02-5215. [↩]
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  20. Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT. Low dietary folate intake is associated with an excess incidence of acute coronary events: The kuopio ischemic heart disease risk factor study. Circulation 2001;103:2674-80. [↩]
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