The Mandatory Fortification of Staple Foods With Folic Acid: A Current Controversy in Germany

Introduction:
The mandatory fortification of staple foods with folic acid to prevent neural tube defects (NTDs) began in the USA in 1998. Since then, more than 50 countries around the world have followed suit.

Methods:
Selective literature review including national study results.

Results and discussion:
Women of child-bearing age need sufficient body stores of folate before conception to prevent folate-sensitive NTDs, which make up 20% to 60% of all NTDs. Merely recommending folic acid supplementation before conception has been found to be an unsuitable strategy. Ingestion of folate-fortified food markedly increases folate intake, generally by about 50% of the recommended daily total intake. In Germany at present, debate surrounds the issue whether folate intake should be raised by mandatory folate supplementation, which will affect the entire population. Folate deficiency is associated with a higher risk of cancer and other diseases; on the other hand, there is concern that very high folic acid intake might promote the growth of pre-neoplastic lesions. There are no consistent study findings to support the latter hypothesis¸ and the evidence for it is derived from research in animals whose folate metabolism differs from that in humans. About 800 pregnancies with NTD are diagnosed each year in Germany; in most cases, the pregnancy is terminated after positive prenatal screening. The incidence of NTDs in Germany is estimated at 12.36 per 10 000 births (a mean figure derived from registry data in Mainz and Saxony-Anhalt) and is thus much higher than the mean incidence across Europe, 7.88 per 10 000 births (EUROCAT data for 2004–2008). Mandatory folic acid fortification should be adopted, as it is a highly effective and inexpensive way to prevent NTDs.

Extracts:
Smoking mothers had significantly lower serum folate concentrations than non-smoking mothers (18.4 vs. 30.6 nmol/L), and the same was true for umbilical cord blood (median 57.1 vs 61.0 nmol/L).
...
For women with a history of neural tube defect–affected pregnancy, a daily intake of 4 to 5 mg folic acid is recommended. However, the lowest effective dose for preventing neural tube defects is not known thus far.

Journal Reference:
“The mandatory fortification of staple foods with folic acid: A current controversy in Germany”, W. Herrmann, R. Obeid, Deutsches Ärzteblatt International|
Volume 108, Issue 15, Pages 249 to 254, doi: 10.3238/arztebl.2011.0249

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High Levels of Folate, from Supplements and Fortification, Are Not Associated with Increased Risk of Colorectal Cancer

Background & Aims:
Folate intake has been inversely associated with colorectal cancer risk in several prospective epidemiologic studies. However, no study fully assessed the influence of the high levels of folate that are frequently consumed in the United States as a result of mandatory folate fortification, which was fully implemented in 1998, and the recent increase in use of folate-containing supplements. There is evidence that consumption of high levels of folic acid, the form of folate used for fortification and in supplements, has different effects on biochemical pathways than natural folates and might promote carcinogenesis.

Methods:
We investigated the association between folate intake and colorectal cancer among 43,512 men and 56,011 women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort; 1,023 were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Cox proportional hazards regression was used to calculate multivariate hazards ratios (RR) and 95% confidence intervals (CI).

Results:
Intake of high levels of natural folate (RRQ5vsQ1=0.86; 95% confidence interval [CI], 0.70–1.06; P -trend=0.12) or folic acid (RRQ5vsQ1=0.84; 95% CI, 0.68–1.03; P -trend=0.06) were not significantly associated with risk of colorectal cancer. Total folate intake was significantly associated with lower risk (RRQ5vsQ1=0.81; 95% CI, 0.66–0.99; P -trend=0.047).

Conclusions:
Intake of high levels of total folate reduces risk of colorectal cancer; there is no evidence that dietary fortification or supplementation with this vitamin increases colorectal cancer risk.


Journal Reference:
High Levels of Folate, from Supplements and Fortification, Are Not Associated with Increased Risk of Colorectal Cancer, Victoria L. Stevens, Marjorie L. McCullough, Juzhong Sun, Eric J. Jacobs, Peter T. Campbell, Susan M. Gapstur, Gastroenterology - 15 April 2011 (10.1053/j.gastro.2011.04.004)