Folic Acid Fortification May Have Lowered Stroke Deaths

"We found evidence of a three-fold acceleration in the decline of stroke-associated mortality that is temporally related to fortification of flour with folic acid," said study investigator Lorenzo D. Botto, M.D., a medical epidemiologist with the Centers for Disease Control and Prevention's National Center on Birth Defects and Developmental Disabilities in Atlanta. "If folic acid fortification is responsible for the improvement in stroke-associated mortality, the public health benefits are substantial."

The research team, led by Dr. Quanhe Yang, estimated that 31,000 stroke-associated deaths and 17,000 deaths related to ischemic heart disease may have been prevented each year since fortification was implemented.

In 1996, the United States Food and Drug Administration required enriched grain products be fortified with folic acid to reduce the risk of neural tube defects in newborns. The researchers hypothesized that fortification might offer a secondary benefit of reducing serum homocysteine concentrations in the population as a whole, which might lead to a decline in death rates due to cardiovascular disease and stroke.

"Many studies have shown that folic acid can lower serum homocysteine levels, and that people with higher-than-average homocysteine levels are at higher risk for stroke and heart disease," Botto said. "We think high homocysteine somehow causes an insult on the vascular wall, weakening the vessel and making it more prone to damage.

The researchers analyzed national death certificate data to assess mortality rates for cardiovascular disease and stroke in the United States among people 40 or older, from 1990 to 2001. They then looked for changes in mortality trends.

The study showed that fortification of flour with folic acid was shortly followed by a doubling of the average serum folate concentration, from 6.6 ng/mL to 15 ng/mL, and an average 14 percent reduction of the serum homocysteine concentration, from 9.6 ìmol/L to 8.3 ìmol/L. As hypothesized, the reduction in homocysteine levels was associated with declining mortality rates due to stroke and cardiovascular disease, Botto said.

Overall, stroke-associated mortality was 10 to 15 percent lower in the three years after fortification (1999-2001), compared with the three years before fortification (1994-96), he said. Before 1997, overall stroke mortality rates declined by about 1 percent per year, compared with 4.5 percent per year after 1997.

"Importantly, the decline in mortality associated with stroke showed a consistent pattern that ran across all genders and racial groups, with improvements for both men and women, whites and blacks," Botto said.

For example, among black men ages 40-59, death rates due to stroke declined by 1.2 percent per year before 1997, compared with 7.4 percent per year after 1997. Among black women 40-59 years, stroke-related mortality declined about 0.7 percent per year before 1997, compared with 3.9 percent per year after 1997.

Among whites of all age groups, the estimated annual percent decline in mortality rates was less than 1 percent before food fortification, but 3 percent or more after food fortification. Researchers observed an improvement in mortality rates due to ischemic heart disease over the same period.

The accelerating improvement in death rates due to stroke and ischemic heart disease could not be explained by changes in other major risk factors, such as cigarette smoking, hypertension, diabetes and total serum cholesterol levels, many of which did not improve or worsen during the period studied, Botto said.

Co-authors include Quanhe Yang, Ph.D. and Jan M. Friedman.