Folate, vitamin B12, homocysteine and prostate cancer risk: a surprise finding

Oct 23, 2004, PSA Rising. Some people assume that the more nutrients and vitamins they consume, the higher their protection against cancer. Is this the case and does it apply to all sectors of the population?

The question comes up especially if people take vitamin supplements in addition to those already in a daily diet and those added to certain processed foods to "fortify" them.

Folate, vitamin B6 and vitamin B12 are involved in homocysteine metabolism. A deficiency of vitamin B12, folate, or vitamin B6 may increase blood levels of homocysteine. Too much homocysteine is related to a higher risk of coronary heart disease, stroke and fatty deposits in peripheral arteries (see American Heart Assoc., Homocysteine, Folic Acid and Cardiovascular Disease, for current advice)

To complicate matters, B vitamins must be kept in balance. Too much folic acid intake (over 1,000 micrograms (µg) can trigger the damaging effects of vitamin B12 deficiency [ 7 ]. In the USA, adults older than 50 years who take a folic acid supplement are recommended to ask their physician or qualified health care provider about their need for vitamin B 12 supplementation. Some people have trouble absorbing vitamin B12 in pill form and need injections.

How do these vitamins relate to prostate cancer? Surprisingly, a team in Sweden has found that higher levels of folate in the blood may be associated with increased risk of a man's developing prostate cancer.

This is surprising because folate not only protects against birth defects and lowers risk of cardiovascular disease -- further, it appears to protect women against breast cancer.

This may not hold true for men's risk of prostate cancer. So far, it's generally accepted that lycopene in tomatoes and in several other fruits and vegetables is protective against prostate cancer. On the face of it it might seem more of any vitamin is better.

And we know from the Harvard long-term study of 32 826 nurses published last year that folate and B6 "may have the potential to be chemopreventive against breast cancer." Ensuring "adequate circulating levels of folate and vitamin B6 by consuming foods that are rich in these nutrients, such as oranges, orange juice, and fortified breakfast cereals, or vitamin supplements," this study concluded, may help reduce risk of breast cancer. Adequate folate levels may be "particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption," the researchers said.

But when the Swedish team compared blood levels of these factors to prostate cancer risk in a prospective study of 254 men with prostate cancer and 514 matched men without known prostate cancer, they found something odd and surprising.

Folate and B12 were expected to be protective against prostate cancer, because folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. Abnormal methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development.

In fact, increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 for folate and 2.63 for vitamin B12 for highest vs. lowest quartile.

Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance.

After adjustment for body mass index and smoking, a statistically significant increased risk remained only for vitamin B12.

"Our results suggest that factors contributing to folate status are not protective against prostate cancer," the researchers write. "On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies."

Folate is high in cooked beans such as fava, kidney, pinto, roman, soy, and white beans, chickpeas, lentils; in cooked leafy green vegetables such as spinach; in asparagus and in romaine lettuce, orange juice, canned pineapple juice and in sunflower seeds. Found also in moderate levels in many other fresh foods from fruits to nuts and meats, folate is also used in North America and Europe to fortify breads and pasta (see this page about Canada)

Vitamin B12, also called cobalamin because it contains the metal cobalt, helps maintain healthy nerve cells and red blood cells. It is also needed to help make DNA, the genetic material in all cells. Vitamin B 12 is bound to the protein in food. Vitamin B 12 is naturally found in animal foods including fish, meat, poultry, eggs, milk, and milk products. Fortified breakfast cereals are a particularly valuable source of vitamin B 12 for vegetarians. (See Table 1 at this National Institutes of Health site for a variety of food sources of vitamin B 12).

Vitamin B12 supplementation is essential for people with pernicious anemia. Older adults, vegetarians and people taking certain medicines may all need supplementary B12.

This article edited by J. Strax. Page last updated Oct 22, 2004; links checked May 26, 2014.

Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: A prospective study. Hultdin J, Van Guelpen B, Bergh A, Hallmans G, Stattin P. Department of Medical Biosciences, Clinical Chemistry, Umea University Hospital, Umea, Sweden. Int J Cancer. 2004 Oct 21 [Epub ahead of print; abstract]

Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. Zhang SM, et al. Department of Epidemiology, Harvard School of Public Health, Division of Preventive Medicine, Boston. Journal of the National Cancer Institute, Vol. 95, No. 5, 373-380, March 5, 2003

Lower Prostate Cancer Risk in Men with Elevated Plasma Lycopene Levels Results of a Prospective Analysis Peter H. Gann et al. Division of Preventive Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School. Cancer Research 59, 1225-1230, March 15, 1999. Full text, free.

Some general information about B Vitamins:

Dietary Supplement Fact Sheet: Vitamin B12 Office of Dietary Supplements • Warren G. Magnuson Clinical Center • National Institutes of Health

Vitamin B12 Deficiency Symptoms