A diet low in folate may increase the risk of developing liver cancer, says a study based in China, highlighting potential additional benefits of folic acid fortification.
"This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and hepatocellular carcinoma," wrote lead author Tania Welzel from the US National Cancer Institute, NIH.
Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.
This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.
While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table.
The new study, published in the journal Cancer Epidemiology, Biomarkers & Prevention, reports that low folate levels may be linked to liver damage and liver cancer, and follows earlier research that reported low levels of the B vitamin may also be linked to increased risk of colorectal cancer and cardiovascular disease.
The researchers recruited 412 patients who tested positive for hepatitis B surface antigen, a marker of hepatitis B infection and therefore at a higher risk of liver damage. Blood levels of folate were measured at the start of the study, with alanine aminotransferase (ALT) and hepatitis B virus DNA levels measured at six-month intervals.
ALT is a measure of liver damage, with low levels found in the blood when the liver is healthy and normal. When the liver is damaged or diseased, ALT is released into the bloodstream, causing increases in blood levels of the enzyme.
Welzel and co-workers report that increased folate levels were associated with lower levels of ALT, with the highest average folate levels associated with a 14 per cent reduction in ALT levels compared to people with the lowest average folate levels.
The patients were followed between 1998 and 2002, and 20 cases of liver cancer (hepatocellular carcinoma) were diagnosed.
When the researchers compared subjects with the lowest average folate levels in red blood cells with all the other subjects, they found that higher red blood cell folate levels were associated with a 67 per cent reduced risk of liver cancer.
More research is needed to support these observations, with prospective studies in other populations needed, and mechanistic studies to elucidate the potential underlying role of folate on liver health.
Liver cancer is the sixth most commonly diagnosed cancer in the world, and third most common cause of death from cancer, according to Cancer Research UK. Despite these figures, the cancer remains relatively rare, with 18,500 new cases in the US every year, and about 3,000 in the UK.
The highest incidences of the disease are in east and Southeast Asia, and middle and eastern Africa. South Central Asia and Northern Europe have the lowest incidence of the disease.
The researchers for the study were affiliated with the National Cancer Institute, Drexel School of Public Health, Fox Chase Cancer Center, Philadelphia, St. James Hospital, Dublin, Fudan Medical University, Shanghai, and Haimen City Center for Disease Control, Haimen City.
Source: Cancer Epidemiology, Biomarkers & Prevention
June 2007, Volume 6, Number 6, Pages 1279-1282
"Blood Folate Levels and Risk of Liver Damage and Hepatocellular Carcinoma in a Prospective High-Risk Cohort"
Authors: Tania M. Welzel, H.A. Katki, L.C. Sakoda, A.A. Evans, W.T. London, G. Chen, S. O'Broin, F.-M. Shen, W.-Y. Lin and K.A. McGlynn