Follow-up on folate and cancer risk

We’ve had a recent comment on our own post regarding the importance of B12 and folate supplementation for people with HIV. The comment expressed concern about some reports that folate may be associated with increased cancer risk. Here’s a reply to that comment:

We recommend this web page for a recent study of folate and REDUCED colorectal cancer risk:

The 2011 article cited, by a well-known nutrition scientist, finds folate from diet and folate from supplements both associated with reduced colorectal cancer incidence–when taken over a long period (we’re talking about 15-20-30 years). This fits with what is generally understood about the value of vegetables in reducing cancer risk. Not surprising to us is the other finding of the study: that short-term folate intake, around the time of the development of pre-cancers, is not going to help reduce cancer incidence! Indeed, many supplements do not necessarily produce pronounced short-term effects, but rather show health benefits over the long term.


Folate (Folic acid) supplementation: a recommendation for acute, continuation and maintenance treatment of depression

Here is a dosage recommendation for supplementation with Folate/Folic acid during the treatment of depression. It’s the conclusion offered by Simon N. Young, Dept. of Psychiatry, McGill University in a 2004 review article:

What about the recommendation that 2 mg of folate be given during the acute, continuation and maintenance treatment of depression? The actual dosage may be debatable; 1 mg may suffice, particularly in countries where there is voluntary or compulsory fortification of food with folate, and the addition of a vitamin B12 supplement may be prudent, but the general principle is reasonable. With our current knowledge, the potential benefits seem to far outweigh any disadvantages.

Reference: Simon N. Young, “Folate and depression—a neglected problem” in J Psychiatry Neurosci. 2007 March; 32(2): 80–82.

For further discussion, see the NYBC entries:


B-Right (B vitamin complex)


Depression and B vitamins – University of Maryland Medical Center’s Complementary Medicine Website

Here’s more on the role of the B Vitamins in depression, together with some common supplementation strategies.

Source: University of Maryland Medical Center’s Complementary Medicine web resource


Studies suggest that vitamin B9 (folate) may be associated with depression more than any other nutrient. Between 15% and 38% of people with depression have low folate levels in their bodies and those with very low levels tend to be the most depressed. Many healthcare providers start by recommending a multivitamin (MVI) that contains folate, and then monitoring the homocysteine levels in the blood to ensure the adequacy of therapy. Elevated homocysteine levels indicate a deficiency of folate even if the levels of folate in the blood are normal. If the MVI alone is not enough to lower homocysteine and improve folate function, the provider may suggest additional folate along with vitamins B6 and B12 to try to bring the homocysteine levels down, thereby eliminating the functional folate deficiency and, hopefully, helping to improve feelings of depression.

Note: NYBC stocks Douglas Lab’s Added Protection Without Iron, a highly bioavailable multivitamin that includes a comprehensive B complex. The no-iron formula is recommended especially if you have elevated liver enzymes or hepatitis.

You can also consider Added Protection With Iron if you want to include iron in your supplements.

Another choice for focusing on the B Vitamins is Jarrow’s B-right, which is especially formulated to provide optimal amounts of folate/folic acid (B-9), B-6 and B-12 for lowering homocysteine levels.

Why Vitamin B12 and Folic Acid (Folate) are important to people with HIV

We’ve adapted this piece from the NYBC Info Sheet on Vitamin B12.

NYBC members often supplement with B-right B complex or with Methylcobalamin, a form of B12 that is better absorbed by the body than other forms of B12.

B-12 may play a very critical role in preventing HIV disease progression: a large Johns Hopkins University study found that people with HIV who are deficient in B-12 have a two-fold increased risk of progression to AIDS. In this study, those who were B-12 deficient progressed to AIDS four years faster than those who were not. The exact mechanism by which adequate B-12 in the body may slow progression is not known, but the finding is not surprising, given all the roles B-12 is known to play in healthy human function.

B12 and another B vitamin, folic acid, are critical to prevent or eliminate the often-overwhelming fatigue that so often accompanies HIV disease, as well as to help prevent some forms of neuropathy and brain and spinal cord changes. Maintaining adequate B12 levels also supports the bone marrow’s production of blood cells (crucial to prevent white and red blood cell decreases), and helps protect the heart.

There are countless anecdotal reports from people with HIV that using B-12 supplementation has dramatically improved their lives by its ability to reverse fatigue, often restoring normal energy to people who had previously been so exhausted that their daily functioning had been greatly affected. Many people have also reported significant improvements in memory and mental functioning, improvements that have made a huge difference in daily life. The possibility that B-12 supplementation might also help prevent or reverse the spinal cord changes that can have such devastating effects on some people is also very encouraging.

B-12 and folic acid should always be given together. Doses of B-12 (1000 mcg given daily via pills, or one to several times weekly via prescribable nasal gel or injections) and folic acid (800 mcg daily via pills) may be useful for restoring energy, treating neuropathy, protecting the heart, increasing overall feelings of well being, and boosting mental function (especially when combined with thiamin, niacin, and folic acid, since all four of these B vitamins are needed for normal neurological function) even when tests don’t indicate obvious deficiencies.

Deficiencies of B-12 can result in deterioration of mental function and neurologic damage that will yield such symptoms as memory loss, decreased reflexes, weakness, fatigue, disorientation, impaired pain perception, tinnitus (chronic ringing in the ears), neuropathy, burning tongue, and various psychiatric disorders. B-12 deficiency can also cause canker sores in the mouth, impaired bone marrow function, loss of appetite, and loss of weight, as well as impaired antibody responses to vaccines.

Folic acid deficiency can also cause fatigue and weakness, along with irritability, cramps, anemia, nausea, loss of appetite, diarrhea, hair loss, mouth and tongue pain, and neurological problems. In addition, folic acid deficiency is believed to play a role in the development of numerous and varied types of human cancers.

A combination of B-12 and folic acid deficiency can allow increases in blood levels of homocysteine, a chemical that can damage artery walls and contribute to heart disease.

One of the known causes of B12 deficiency is chronic viral illness with resulting poor gastrointestinal absorption. AZT use may contribute to deficiencies of both B-12 and folic acid. Many other drugs may worsen folate status in the body including TMP/SMX (Bactrim, Septra), pyrimethamine, and methotrexate (all three of which are folate antagonists), as well as phenytoin (Dilantin), various barbiturates, and alcohol (all of which block folate absorption). B-12 deficiency can also worsen folate levels in the body because B-12 is required to change folate into its active form.

Folic acid/folate (Vitamin B9) to protect against development of cancer

The University of Maryland Medical Center’s website on Complementary Medicine (a clearly written, up-to-date resource, by the way) provides this review of folic acid (also known as folate or Vitamin B9) as a supplement protecting against the development of cancers. The strongest evidence appears to be for folic acid’s ability to protect against colorectal and breast cancers. In our excerpt below, we have highlighted two significant passages.

For recommendations on how to take this supplement (you may be getting it in a multivitamin or a B-complex supplement), see the NYBC entry on Folic Acid.

Folic acid appears to protect against the development of some forms of cancer, particularly cancer of the colon, as well as breast, esophagus, and stomach, although the information regarding stomach cancer is more mixed. It is not clear exactly how folate might help prevent cancer. Some researchers speculate that folic acid keeps DNA (the genetic material in cells) healthy and prevents mutations that can lead to cancer.

Population-based studies have found that colorectal cancer is less common among individuals with very high dietary intakes of folic acid. The reverse appears to be true as well: low folic acid intake increases risk of colorectal tumors. To have a significant effect on reducing the risk of colorectal cancer, it appears that at least 400 mcg of folic acid per day over the course of at least 15 years is required. Similarly, many clinicians recommend folic acid supplementation to people who are at high risk for colon cancer (for example, people with a strong family history of colon cancer).

Similarly, one population-based study also found that cancers of the stomach and esophagus are less common among individuals with high intakes of folic acid. Researchers interviewed 1095 patients with cancer of the esophagus or stomach as well as 687 individuals who were free of cancer in three health centers across the United States. They found that patients who consumed high amounts of fiber, beta-carotene, folic acid, and vitamin C (all found primarily in plant-based foods) were significantly less likely to develop cancer of the esophagus or stomach than those who consumed low amounts of these nutrients. Another important, good-sized study, however, did not find any connection between folic acid intake and stomach cancer. The possibility of some protection from folate against stomach cancer in particular needs clarification and, therefore, more research is warranted.

Low dietary intake of folate may increase the risk of developing breast cancer, particularly for women who drink alcohol. Regular use of alcohol (more than 1 ½ to 2 glasses per day) is associated with increased risk of breast cancer. One extremely large study, involving over 50,000 women who were followed over time, suggests that adequate intake of folate may lessen the risk of breast cancer associated with alcohol.

Vitamin B12 deficiency in older adults; Vitamin B12, Vitamin B6, and folate supplements under study to lower risk of cardiovascular disease

This excerpt from the Office of Dietary Supplements – National Institutes of Health Fact Sheet on Vitamin B12 discusses why older adults (people over 50) may need to take supplements or use fortified foods to prevent Vitamin B12 deficiency:

Hydrochloric acid helps release vitamin B12 from the protein in food. This must occur before vitamin B12 binds with intrinsic factor and is absorbed in your intestines. Atrophic gastritis, which is an inflammation of the stomach, decreases the secretion of gastric juices, including hydrochloric acid. Less hydrochloric acid decreases the amount of vitamin B12 separated from proteins in foods and can result in poor absorption of vitamin B12. Decreased hydrochloric acid secretion also results in growth of normal bacteria in the small intestines. The bacteria may take up vitamin B12 for their own use, further contributing to a vitamin B12 deficiency. Up to 30 percent of adults aged 50 years and older may have atrophic gastritis, an increased growth of intestinal bacteria, and be unable to normally absorb vitamin B12 in food. They are, however, able to absorb the synthetic vitamin B12 added to fortified foods and dietary supplements. Vitamin supplements and fortified foods may be the best sources of vitamin B12 for adults older than age 50 years.

Caution: Folic Acid and vitamin B12 deficiency
Folic acid can correct the anemia that is caused by vitamin B12 deficiency. Unfortunately, folic acid will not correct the nerve damage also caused by vitamin B12 deficiency [1,36]. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. Folic acid intake from food and supplements should not exceed 1,000 μg daily in healthy individuals because large amounts of folic acid can trigger the damaging effects of vitamin B12 deficiency [7]. Adults older than 50 years who take a folic acid supplement should ask their physician or qualified health care provider about their need for additional vitamin B12.

A further excerpt from the ODS Vitamin B12 Info Sheet discusses the relationship between vitamin B12, homocysteine, and cardiovascular disease. As noted, “clinical intervention trials are underway to determine whether folic acid, vitamin B12, and vitamin B6 supplements can lower risk of coronary heart 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 United States, and is on the rise in developing countries. The National Heart, Lung, and Blood Institute of the National Institutes 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 diabetes. 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. Elevated homocysteine levels may impair endothelial vasomotor function, which determines how easily blood flows through blood vessels. 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.

Vitamin B12, folate, and vitamin B6 are involved in homocysteine metabolism. In fact, a deficiency of vitamin B12, folate, or vitamin B6 may increase blood levels of homocysteine. Recent studies found that vitamin B12 and folic acid supplements decreased homocysteine levels in subjects with vascular disease and in young adult women. The most significant drop in homocysteine level was seen when folic acid was taken alone. A significant decrease in homocysteine levels also occurred in older men and women who took a multivitamin/ multimineral supplement for 8 weeks. The supplement taken provided 100% of Daily Values (DVs) for nutrients in the supplement.

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

Supplementing with B Vitamins to counter depression

Although we’ve given a lot of attention to supplements that have been studied specifically for depression, such as SAM-e, DHEA, St. John’s Wort, Tryptophan, and 5-HTP, this note from the University of Maryland Medical Center’s Complementary Medicine website reminded us of the importance of looking at general nutritional status in assessing and responding to complex health conditions like depression. In this case, it’s a suggestion that supplementing with B Vitamins can have an impact on depressive symptoms.

See additional information in NYBC’s entry on its B Vitamin supplement.

Studies suggest that vitamin B9 (folate) may be associated with depression more than any other nutrient. Between 15% and 38% of people with depression have low folate levels in their bodies and those with very low levels tend to be the most depressed. Low folate levels tend to lead to elevated homocysteine levels. Many healthcare providers recommend a B complex multivitamin that contains folate as well as vitamins B6 and B12 to improve symptoms. If the multivitamin with these B vitamins is not enough to bring elevated homocysteine levels down, the physician may then recommend higher amounts of folate along with vitamins B6 and B12. Again, these three nutrients work closely together to bring down high homocysteine levels, which may be related to the development of depression.