Salt in the Diet: Too Much, Too Little, Just Right?

More Data, More Questions on Sodium and Cardiovascular Risk

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Questions continue to plague recommendations for daily sodium intake. Recently, both high and low sodium levels have been linked to increased cardiovascular risk in patients with established cardiovascular disease.

“We know that high sodium is certainly bad for you,” said Andrew Mente, PhD, assistant professor of clinical epidemiology and biostatistics at McMaster University in Hamilton, Ontario, Canada. “What’s interesting is that we also found that too little sodium was also a significant predictor of increased cardiovascular events.”

Mente and Martin J. O’Donnell, MB, PhD, associate professor of medicine at McMaster, published their findings in The Journal of the American Medical Association (JAMA).

High risk at both ends of the sodium range

Mente and McDonnell found a “J-shaped” relationship that included a fairly wide range of high but “normal” sodium levels without excess cardiovascular event rates. The findings may have implications for the management of patients at high cardiovascular risk, including those with kidney disease.

The researchers analyzed observational data on nearly 29,000 patients from two randomized trials of telmisartan: ONTARGET and TRANSCEND.

“These were people at high risk for cardiovascular disease, followed up for hard cardiovascular outcomes for an average of almost five years,” said Mente.

At a 24-hour sodium excretion rate of less than 3 g/day, the investigators found increased rates of cardiovascular mortality and hospitalization from heart failure. There was also a higher burden of cardiovascular disease associated with high sodium excretion—but not until levels of greater than 6.5 g/day.

Stroke risk fell as 24-hour potassium excretion increased. There were no significant interactions between sodium and potassium excretion.

“What I found interesting is that the J-shaped curve described in this study shows increased risks starting at sodium levels of less than 3 g and more than 7 g, respectively,” said Daniel Batlle, MD, professor of medicine at Northwestern University Feinberg School of Medicine and a nephrologist at Northwestern Memorial Hospital, Chicago.

“The ‘safe’ range where there are no excess cardiovascular events based on this study happens to be a wide one: from 3 to 7 g of urinary sodium,” Batlle said. “This would encompass the average intake of sodium of most Americans—which is considered to be too high, based on current thinking.”

A growing body of evidence

Other studies have reported similar relationships, Mente said. He cited the population-based European Project on Genes in Hypertension study—published in JAMA last spring—which also linked lower sodium to higher cardiovascular mortality.

“Some people saw that study and said, ‘Well, these are people that are healthy. If we were to look at patients with cardiovascular disease, we’re not going to find low sodium puts them at higher risk,” he said. “But indeed, we found actually that same relationship.”

Lowering sodium intake is a major focus of efforts to reduce cardiovascular risk. The current World Health Organization recommendation is less than 2 g/day. The American Heart Association advises the public, “Aim to eat less than 1500 milligrams of sodium per day.”

It’s especially important to clarify optimal sodium intake for patients with existing cardiovascular disease —many of whom also have chronic kidney disease—who may be more vulnerable to the effects of high and low sodium.

While most experts emphasize the importance of reinforcing advice not to eat too much salt, the evidence raises the possibility that current recommendations for sodium restriction could be causing patient harm. “Do we keep people doing what they are doing anyhow?” asked Batlle. “One could interpret the data in this way: ‘Why put people on a low-salt diet when better results are seen with what we consider a normal-salt diet in the first place?’

“I am not ready to conclude at all that that’s what doctors should be recommending for their patients, but this is one potential interpretation.”

A key limitation of the most recent JAMA study was that sodium and potassium excretion were estimated from spot urine samples. “We all would agree that the way sodium was measured in the urine is not precise,” said Batlle. “But having said that, the results are very thought-provoking and should be the impetus for further study, including dietary intake of sodium and potassium assessed with a timed urine collection over 24 hours.”

Intriguing speculations on mechanisms

The increase in heart failure may provide a clue as to one possible mechanism by which low sodium might lead to high cardiovascular risk.

“There is some evidence that low sodium intake can trigger activation of the renin-angiotensin system and increase sympathetic nervous system activity—which is not a favorable response from a cardiovascular standpoint,” said Mente.

Other studies suggest that low sodium intake can affect lipoproteins and insulin resistance and lead to a negative balance of magnesium and calcium. “So there are all these other potential unintended consequences,” Mente said.

So what’s the next step on sodium and cardiovascular risk?

“Certainly to answer the question definitively, we eventually need to do a randomized controlled trial,” said Mente. “And not with surrogate measures like blood pressure, but with ‘hard’ cardiovascular disease events. But that’s a challenging study in itself, because you need to get people to eat a very low sodium diet for a long period of time.”

He added, “Taking the evidence in its totality, perhaps instead we should be focusing on improving the overall quality of the diet, rather than focusing on a single nutrient like sodium. Also, a high-quality diet is much more palatable and easier to maintain in the long term, and would have universal benefits beyond cardiovascular disease.”