Folic acid increase appears to have cut stroke deaths

Fortifying enriched grain products with folic acid in the 1990s appears to have been followed by a decline in stroke and ischemic heart disease deaths, US government researchers reported at an American Heart Association conference last week.

The researchers 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.

While the program, initiated by the Food and Drug Administration in 1996, was designed to reduce the risk of neural tube defects in newborns, researchers predicted that it could have had a secondary benefit of reducing serum homocysteine concentrations in the population as a whole.

Homocysteine is thought to be a marker for cardiovascular disease and several studies have shown that folic acid can lower serum homocysteine levels. There is also evidence that people with higher-than-average homocysteine levels are at higher risk for stroke and heart disease.

"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, 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," he added.

Many experts believe Europe should follow the example set by the US, Canada and Chile, countries that have all mandated folic acid fortification. However European governments have been reluctant to launch such a campaign, with the UK recently citing a lack of evidence of possible negative effects on the elderly. Yet Europe's national food safety agencies recently announced a plan to explore ways of reducing folic acid deficiency among women of child bearing age, which could include promotion of fortified foods.

The US researchers analyzed national death certificate data to assess mortality rates for cardiovascular disease and stroke in the United States among people aged 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 per cent 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.

"We think high homocysteine somehow causes an insult on the vascular wall, weakening the vessel and making it more prone to damage," he explained.

Overall, stroke-associated mortality was 10 to 15 per cent 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 per cent per year, compared with 4.5 per cent 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 aged 40-59, death rates due to stroke declined by 1.2 per cent per year before 1997, compared with 7.4 per cent per year after 1997. Among black women aged 40-59 years, stroke-related mortality declined about 0.7 per cent per year before 1997, compared with 3.9 per cent per year after 1997.

Among whites of all age groups, the estimated annual per cent decline in mortality rates was less than 1 per cent before food fortification, but 3 per cent or more after food fortification. Researchers observed an improvement in mortality rates due to ischaemic 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.

The researcher presented the findings at the annual Conference on Cardiovascular Disease Epidemiology and Prevention in San Fransisco last week.