Published: Apr 6, 2014 | Updated: Apr 6, 2014
By Todd Neale, Senior Staff Writer, MedPage Today

• This meta-analysis evaluated the relationship between individual measures of dietary sodium intake versus outcome, in cohort studies and randomized controlled trials.
• Investigators found a U-shaped association such that both low sodium intakes and high sodium intakes were associated with increased mortality.
• At issue is the definition of usual intake 2,645 to 4,945 mg per day, which are levels that the American Heart Association claims are dangerous and associated with hypertension and other cardiovascular conditions.

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A new analysis suggested that most people around the world are consuming just the right amount of sodium, although the American Heart Association questioned the findings.

Compared with an intake of 2,645 to 4,945 mg per day — the usual sodium intake range for 90% of the world’s population — higher sodium consumption was associated with greater risks of all-cause mortality (HR 1.16, 95% CI 1.03-1.30) and cardiovascular disease events (HR 1.12, 95% CI 1.02-1.24), according to Niels Graudal, MD, of Rigshospitalet-Copenhagen University Hospital, and colleagues.

But consuming too little sodium was tied to worse outcomes, too; compared with consuming less than 2,645 mg per day, usual intakes were associated with lower risks of death (HR 0.91, 95% CI 0.82-0.99) and cardiovascular disease events (HR 0.90, 95% CI 0.82-0.99), the researchers reported online in the American Journal of Hypertension.

“The findings here lend support to those who have questioned the scientific basis for sodium reduction [recommendations], which are based primarily on the assumed blood pressure effect obtained in selected intervention studies and a selected meta-analysis of intervention studies,” the authors wrote, pointing to a Cochrane review published in 2004 that showed reductions in blood pressure with modest reductions in salt intake in individuals with either elevated or normal blood pressure.

“However, the blood pressure effect is proportional to the baseline blood pressure, and because the baseline blood pressure in these intervention studies and the meta-analysis was much higher (approximately 130/85 mm Hg) than the mean blood pressure of the normotensive population (116/69 mm Hg) and the general population (122/71 mm Hg), the association of salt intake with blood pressure is overestimated,” they continued. “Furthermore, the meta-analysis downplays other surrogate markers (hormones, lipids), which previously have been shown to increase during sodium reduction and thus have the potential to adversely affect outcomes.”

Salt Restriction Controversy

The issue of sodium restriction to improve health outcomes — particularly through reductions in blood pressure leading to lower risks of myocardial infarction and stroke — has been controversial over the past decade.

In 2004, the Institute of Medicine (IOM) defined the tolerable upper level of sodium intake per day as 2,300 mg, with an adequate level defined as 1,200 to 1,500 mg. Since then, several organizations have recommended reducing sodium intake to those levels.

“However, these definitions were inconsistent with IOM’s own definition of adequate intake, which is ‘the approximate intake found in apparently healthy populations,'” Graudal and colleagues wrote. “Because the mean intake of sodium in populations ranges between approximately 2,700 mg and 4,900 mg, conventional estimates of adequate intake and tolerable upper intake level would have been similar to these values.”

Also, some studies published in recent years have called into question the benefits of reducing sodium intake. An updated Cochrane review released in 2011, for example, showed that pooled data on about 6,500 participants in clinical trials did not demonstrate a significant effect from sodium restriction on mortality or cardiovascular disease, either in those with normal blood pressure or those who were hypertensive.

Last year, the IOM revisited the issue at the request of the CDC, issuing a report that concluded that there was insufficient evidence to conclude whether reducing daily sodium intake to less than 2,300 mg leads to lower or higher risks of cardiovascular events and death.

“Our study extends the IOM report by identifying a specific range of sodium intake (2,645 to 4,945 mg) associated with the most favorable health outcomes, within which variation in sodium intake is not associated with variation in mortality,” Graudal and colleagues wrote. “Moreover, this optimal range of intake, based upon available evidence, is coterminous with the current dietary intake of most of the world’s population and is in accordance with the IOM rules for definition of an adequate intake and tolerable upper intake level of sodium.”

American Heart Association Responds

After the latest IOM report was released, the American Heart Association — whichrecommends consuming less than 1,500 mg of sodium each day — defended its stance.

“Given the abundance we have about excess sodium in diet and its relationship to hypertension and the ability of us as health professionals to recommend to patients that if they lower their blood pressure they will reduce their risk of heart disease and stroke, we are not distracted by these analyses [by the IOM] that have significant methodological flaws,”Elliott Antman, MD, a cardiologist at Brigham and Women’s Hospital in Boston and president-elect of the AHA, told MedPage Today at the time.

And the AHA continued to stand behind its recommendation in response to the current analysis by Graudal and colleagues.

“There is a significant body of scientific research that proves a very dangerous association between sodium intake and significant health problems, including in some cases even death. I wish we could say sodium intake does not matter that much to your health, but it does,” AHA CEO Nancy Brown said in a statement.

“Millions of Americans consume too much sodium and as a result face increased risk for high blood pressure, stroke, and other very serious conditions. Based on decades of scientifically sound research, we simply cannot minimize the impact of excess sodium in the diet,” she continued, pointing out that about 90% of all U.S. adults will develop hypertension at some point.

“American Heart Association volunteer and staff scientists have found flaws in several of the studies that were used in this newly published research. In fact, we published a Scientific Advisory in February that detailed some of this problematic research that could lead to contradictory findings,” Brown said. “In short, this new analysis of these studies should not be used as rationale to reverse public health policy recommendations.”

The Study

Graudal and colleagues examined data from 23 cohort studies and two follow-up studies of randomized trials that included a total of 274,683 participants.

Daily sodium intake was defined as low (less than 2,645 mg), usual (2,645 to 4,945 mg), or high (more than 4,945 mg). The usual intake was based on prior data showing that sodium consumption fell within that range for 90% of the world’s population.

Usual sodium intake was associated with lower risks of all-cause mortality and cardiovascular events compared with low intake, but there were no differences for stroke or heart disease.

High sodium intake was associated with greater risks of all-cause mortality, cardiovascular events, stroke, and heart disease compared with usual intake overall, although the stroke risk was significant only in Japanese populations.

When the researchers restricted their analyses to population-representative samples with adjustment for multiple confounders, the lower risk of all-cause mortality seen with usual versus low sodium intake remained significant (HR 0.86, 95% CI 0.81-0.92). However high sodium intake was no longer associated with all-cause mortality when compared with usual intake (HR 1.04, 95% CI 0.91-1.18).

The researchers also explored whether there were differences in the relationships seen with usual intakes in the upper versus the lower half of the range, and didn’t find any.

They acknowledged that their analysis was limited by the inaccurate measurement of sodium intake in the included studies.

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