Health Impact of Fortification

There is scientific consensus that there is no evidence that consuming foods fortified with folic acid has a negative impact on health. 

When considering mandatory fortification of cereal grains with folic acid, several governments have had scientific committees closely review available evidence on the safety of fortifying food with folic acid. These panels found no harmful effects of consuming foods fortified with folic acid. Five of the reports concluded that the benefits of fortifying with folic acid outweigh potential unforeseen risks. One report from the European Union concluded there was insufficient information to conduct a full risk assessment.

Some studies have linked high folate consumption (greater than 669 mcg/day) to colorectal [7] and prostate cancers [8]. However, researchers have not found clear evidence that higher levels of folate, either from dietary folate or from folic acid via fortification or supplementation, at the recommended amount (400 mcg/day) cause tumors to grow [9,10].   

Furthermore, there is a scientific consensus that folate deficiency leads to negative DNA methylation changes that contribute to the development of cancer, and that folic acid protects against the formation of cancer cells [9,11]. 

Learn more: The Safety of Fortifying with Folic Acid (FFI) 

References: 

1. Scientific Advisory Committee on Nutrition. Folate and Disease Prevention. 2006. ​ 
2. Food Standards Australia New Zealand. Final Assessment Report, Proposal P295, Consideration of Mandatory Fortification with Folic Acid. 4 October 2006. ​ 
3. Food Safety Authority of Ireland. Report of the National Committee on Folic Acid Food Fortification. 2006. ​ 
4. Health Council of the Netherlands. Towards an optimal use of folic acid. 21 February 2008. ​ 
5. European Food Safety Authority (EFSA). ESCO REPORT: Prepared by the EFSA Scientific Cooperation Working Group on Analysis of Risks and Benefits of Fortification of Food with Folic Acid. 6 October 2009. ​ 
6. Office of the Prime Minister’s Chief Science Advisor. The Health Benefits and Risks of Folic Acid Fortification of Food, A report by the Office of the Prime Minister’s Chief Science Advisor and the Royal Society Te Apārangi. June 2018. ​ 
7. Wien TN, et al. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open. 2012 Jan 12;2(1):e000653. 
8. Rycyna KJ, et al. Opposing roles of folate in prostate cancer. Urology. 2013 Dec;82(6):1197-203. 
9. Field MS, Stover PJ. Safety of folic acid. Annals of the New York Academy of Sciences. 2018;1414(1):59–71. 
10. US National Institutes of Health Office of Dietary Supplements. “Folate.” Accessed 23 December 2025. 
11. Maruvada P, et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. American Journal of Clinical Nutrition. 2020;112(5):1390–1403. 

Cerebral folate deficiency (CFD) is an extremely rare neurological disease where folate is prevented from entering the nervous system, despite normal blood levels. CFD should not be treated with folic acid, as folic acid will compete with other folate forms (e.g., folinic acid) that can treat the condition.  

CFD is a serious condition that requires treatment from healthcare professionals, who will advise whether a treatment plan requires diet modification (e.g., removing cow’s milk from the diet to avoid proteins that block folate receptors or avoiding fortified foods).  

Reference: 

Hyland K, Shoffner J., & Heales S. J. Cerebral folate deficiency. Journal of Inherited Metabolic Disease. 2010;33(5): 563–570. 

Children and pregnant and lactating women especially benefit from consuming fortified foods as they require high levels of vitamins and minerals to support physical growth and the development of new tissues. When many fortified foods reach the same population, a country may want to conduct a comprehensive analysis of food consumption to ensure that the population is not consuming excessive levels of nutrients.

For example, United States residents have access to folic acid in foods made with enriched flour, breakfast cereals that are voluntarily fortified, and through easily-accessible vitamin supplements. Yet a study found that only 2.7% of the adult population consumed excessive levels of folic acid, and only people who took high-dose supplements reach the high levels.

There is limited research around the effect of unmetabolized folic acid and its relationship to autism. Unmetabolized folic acid occurs when there is more folic acid in the bloodstream than the liver can process at a given time. As a water-soluble vitamin, any unmetabolized folic acid is excreted in urine. One study that examined fetal exposure to different folate forms found a dose-response relationship between unmetabolized folic acid and risk of autism spectrum disorder in Black children [1]. The researchers recognized the continued importance of adequate folic acid during pregnancy while also calling for further research. 

In the study, the pregnant women with high unmetabolized folic acid in their blood reported taking prenatal supplements providing ~800 mcg/day of folic acid. This is double the recommended amount; the United States Centers for Disease Control and Prevention recommends that women who are pregnant or could become pregnant consume 400 mcg of folic acid a day [2]. 

A properly designed fortification program following WHO guidelines for fortifying wheat flour and maize flour will not deliver high-dose supplement-equivalent amounts of folic acid.  Further, a supplement is a high dose delivered at once; folic acid added in fortified food will enter the bloodstream throughout the day as food is consumed. Folic acid fortification is one of the safest and most effective ways to prevent folate deficiency and its health consequences, including cardiovascular disease, neural tube defects, and anemia.  

References: 

1. Raghavan, R, et al. A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder. The American Journal of Clinical Nutrition. 2020;112(5):1304-1317. 
2. United States Centers for Disease Control and Prevention. About Folic Acid. Accessed 11 November 2025. https://www.cdc.gov/folic-acid/about/index.html. 

With the procedures that doctors use today to diagnose vitamin B12 deficiency, folic acid fortification or supplementation does not mask vitamin B12 deficiency.  Vitamin B12 deficiency is now diagnosed with serum indicators (serum B12) rather than diagnosed by megaloblastic anemia, as it was in the past. When megaloblastic anemia is used to diagnose vitamin B12 deficiency, consuming folic acid supplements or fortified foods can mask the presence of vitamin B12 deficiency. 

Megaloblastic anemia is a blood disorder that occurs when the bone marrow produces stem cells that form abnormally large red blood cells due to insufficient intake of vitamin B12 and/or vitamin B9 (folate). FFI supports efforts to improve the prevention, diagnosis, and treatment of vitamin B12 deficiency. 

Reference: 

Field MS, Stover PJ. Safety of folic acid. Annals of the New York Academy of Sciences. 2018;1414(1):59–71. 

No side effects on health have been reported in the studies published on fortified rice or wheat and maize flour.

Wheat, maize, and rice are natural sources of the following minerals: calcium, phosphorus, zinc, iron, and copper.

They are also natural sources of the following B vitamins: folate (B9), thiamin (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), and biotin (B7).

Source: Bauernfeind and DeRitter, Nutrient Additions to Food

Nutrients in cereal grains are mainly in the outer layers, and these are discarded as the grain is milled. Fortifying returns the lost nutrients, but simply restoring the nutrients may not be enough to make a health impact in populations where deficiencies have been identified. Appropriately fortifying grains with additional amounts of vitamins and minerals can improve public health.

This is different in every country. Global guidelines are available for wheat fortification, but each country is encouraged to consider its unique nutritional needs to establish fortification standards. Another consideration in setting standards is whether other staple foods are fortified. For example, if a country fortifies cooking oil with vitamin A, it might not include vitamin A in fortified wheat flour.

The most common nutrients added to flour are iron and folic acid, a form of vitamin B9. Other vitamins commonly added to flour are thiamin, riboflavin, and niacin. Likewise, rice is commonly fortified with iron and most of the B vitamins. Riboflavin (vitamin B2) is usually not added to rice because its orange color changes the appearance of rice.

The following table shows the types of common nutrients and their compound form that are used in fortification of cereal grains:

• Vitamin A: Vitamin A Palmitate water dispersible, spray dried stabilized; Vitamin A Acetate water dispersible spray dried, stabilized
• Vitamin B group: B1 Thiamine Mononitrate, B2 Riboflavin Hydrochloride, B3 Niacin or Nicotinamide, B5 Calcium Panthothenate, B6 Pyridoxine hydrochloride, B9 Folic acid, B12 Cyanocobalamin 0.1% or 1% spray dried
• Vitamin D: D3 Cholecalciferol
• Calcium: Calcium Carbonate, Calcium Sulphate
• Iron: For flours: Sodium Iron EDTA, Ferrous Sulfate, Ferrous Fumarate, Electrolytic Iron powder For rice: Ferric pyrophosphate
• Zinc: Zinc Oxide, Zinc Sulphate

This is different in every country. Some factors to consider in determining the amount of each nutrient to include in fortification are:

• Vitamin and mineral deficiency among the population
• Average flour/rice consumption
• The body’s ability to absorb the vitamin or mineral compound
• Effect on the food’s sensory properties
• Ongoing cost to buy premix of vitamins and minerals for fortification

Fortifying flour with iron has been shown to improve iron status among specific populations in at least four countries: China, Iran, Venezuela, and Fiji. Many countries with fortification programs, however, do not measure iron status before and after fortification. Eight sub-national studies have found that fortifying flour with folic acid reduced the incidence of neural tube birth defects such as spina bifida by 31% to 78%.

Several controlled research studies conducted in children and young women have demonstrated that regular consumption of rice fortified with adequate levels of easily absorbed nutrients results in a significant reduction in the prevalence of micronutrient deficiencies.

When appropriate levels of easily absorbed iron are used, fortification can impact iron status within 12 months after the program is fully implemented if the vulnerable population consumes fortified products daily. As it takes time for programs to be fully operational, fortification leaders estimate it may be three years between fortification’s initiation and a nutritional impact on iron status.

With folic acid, changes in folate status may be observed within 3 to 4 months after fortification is fully implemented. It will take at least 12 months to see an impact on neural tube defects because women need to be consuming folic acid at the time they conceive to prevent these birth defects.