Vitamin B9 (Folic acid) Disease Prevention - Part 2

Cancer

Cancer is thought to arise from DNA damage in excess of ongoing DNA repair and/or the inappropriate expression of critical genes. Because of the important roles played by folate in DNA and RNA synthesis and methylation it is possible for folate intake to affect both DNA repair and gene expression. The consumption of at least five servings of fruits and vegetables daily has been consistently associated with a decreased incidence of cancer. Fruits and vegetables are excellent sources of folate, which may play a role in their anti-carcinogenic effect. Observational studies have found diminished folate status to be associated with cancers of the cervix, colon and rectum, lung, esophagus, brain, pancreas, and breast. Intervention trials in humans have been conducted mainly with respect to cervical and colorectal (colon and rectal) cancer. While the results in cervical cancer have been inconsistent, randomized intervention trials regarding colorectal cancer have been very promising.

Colorectal cancer: The role of folate in preventing colorectal cancer provides an example of the complexity of the interactions between genetics and the nutritional environment. In general, observational studies have found relatively low folate intake and high alcohol intake to be associated with increased incidence of colorectal cancer. Alcohol interferes with the absorption and metabolism of folate. In a prospective study of more than 45,000 male health professionals, current intake of more than two alcoholic drinks per day doubled the risk of colon cancer. The combination of high alcohol and low folate intake yielded an even greater risk of colon cancer. However, increased alcohol intake in individuals who consumed 650 mcg or more of folate per day was not associated with an increased risk of colon cancer. In some studies, individuals who are homozygous for the C677T MTHFR polymorphism (TT) have been found to be at decreased risk for colon cancer when folate intake is adequate. However, when folate intake is low and/or alcohol intake is high individuals with the (T/T) genotype have been found to be at increased risk of colorectal cancer.

Breast cancer: A number of prospective studies have found that even moderate alcohol intake is associated with an increased risk of breast cancer in women. Recently, the results of two prospective studies suggested that increased folate intake may reduce the risk of breast cancer in women who regularly consume alcohol. A very large prospective study of over 88,000 nurses found no relationship between folic acid intake and breast cancer in women who consumed less than one alcoholic drink per day. However, in those women consuming at least one alcoholic drink per day, folic acid intake of at least 600 mcg daily resulted in about half the risk of breast cancer compared with women who consumed less that 300 mcg of folic acid daily.

Alzheimer's disease and cognitive impairment

The role of folate in nucleic acid synthesis and methylation reactions is essential for normal brain function. Over the past decade several investigators have described associations between decreased folate levels and cognitive impairment in the elderly. A large cross-sectional study of elderly Canadians found that those individuals with low folate levels were more likely to have dementia, be institutionalized, and be depressed. However, these findings could reflect the poorer nutritional status of institutionalized elderly and individuals with dementia. In the same study, low folate levels were associated with an increased likelihood of short-term memory problems in elderly individuals who did not show signs of dementia. In a recent study of 30 elderly nuns, who lived in the same convent, ate the same diet, and had similar lifestyles, researchers found a strong association between decreased blood folate levels and the severity of brain atrophy related to Alzheimer's disease after their deaths. Moderately increased homocysteine levels, as well as decreased folate and vitamin B12 levels have also been associated with Alzheimer's disease and vascular dementia. Low serum vitamin B12 (< 150 pmol/L) or folate (< 10 nmol/L) levels were associated with a doubling of the risk of developing Alzheimer's disease in 370 elderly men and women followed over 3 years. In a sample of 1,092 men and women without dementia followed for an average for 10 years, those with higher plasma homocysteine levels at baseline had a significantly higher risk of developing Alzheimer's disease and other types of dementia. Those with plasma homocysteine levels greater than 14 micoromoles/liter had nearly double the risk of developing Alzheimer's disease.