When Dr. Salim Yusuf began publishing research and commentaries a decade ago suggesting that sharp reductions in salt intake don’t improve heart health, the medical world sat up and took notice.
Not only did the work contradict years of conventional wisdom, but Yusuf is among this country’s most celebrated cardiovascular scientists, an Order of Canada member and one of the top 20 most-cited health researchers ever.
The salt papers were published in some of the world’s foremost medical journals. Much of the attention they attracted, though, was less than flattering.
An international group of scientists recently accused the McMaster University professor and his collaborators of conducting fatally flawed studies, with findings that are further tainted by conflicts of interest with the drug and food industries.
The research has slowed efforts to get people to consume less sodium, a leading trigger of high blood pressure and the harm it causes, they say.
The critics group, led by Dr. Norman Campbell of the University of Calgary, recently took the complaints to a surprising new level, asking Jean-Yves Duclos, the federal health minister, to launch an inquiry into the work by Yusuf and his colleagues and alerting McMaster to its concerns.
Their efforts have not exactly borne fruit. Yusuf was just awarded the Canada Council’s $100,000 Killam prize for research excellence, the agency calling him “among the most accomplished medical researchers in the world.”
The Campbell group demanded that the prize be revoked. It was not. Meanwhile, Health Canada says it never even received the letter asking for an inquiry.
But debate over the issue continues, both sides convinced they’re right, guidelines on heart healthy diets perhaps hanging in the balance.
“They’re making inaccurate and false statements and misleading statements and misinterpretations and they’re not correcting things that are obviously flawed,” said Campbell in an interview. “This is a global aggravation for people who are trying to improve the health of their populations.”
In a paper published last October, he and 24 colleagues from Harvard to Johns Hopkins and the University of London, lambasted the McMaster research. Some scientists have “propagated a myth” that curbing sodium does not steadily reduce cardiovascular disease, they said, while noting pointedly that salt is an important profit-maker for the food industry.
But Yusuf and his colleagues say they’re bewildered by the fierce opposition their ideas have provoked. It seems like a case of scholars with entrenched opinions refusing to seriously consider evidence that challenges the status quo, they say.
To ask politicians now to intervene in what is essentially a scientific debate is wholly unwarranted, said Yusuf. He only learned about the request for a federal investigation when informed by the National Post.
“It’s almost like a vendetta,” he said. “I don’t know what the basis of this is…. It’s just mudslinging, there’s nothing in it at all.”
Health Canada said it could not comment on the call for an inquiry because it failed to receive the request, though the senders say other recipients copied on the same email did.
Ironically, both sides agree on one fact: excessive consumption of salt and other forms of sodium is dangerously unhealthy.
The more sodium humans take in, the more water the body retains to essentially wash it away, which in turn boosts the pressure at which blood is pushed through arteries and veins. And high blood pressure leads to heart attacks, strokes and death. In fact, hypertension has been called the world’s leading cause of mortality, with sodium a culprit in as many as 30 per cent of cases.
The difference of opinion comes down to exactly what constitutes too much sodium. And at the heart of that disagreement is a fight, oddly enough, over urine — or at least how it should be tested to accurately measure sodium intake.
Relying on the conventional scientific wisdom, the World Health Organization recommends consuming less than two grams of sodium — five grams of salt — a day. Health Canada, the Mayo Clinic and other health bodies suggest no more each day than 2.3 grams, about a teaspoon of salt.
A 2017 Health Canada report estimated the average intake in this country was 2.8 grams.
Underpinning those recommendations are studies like the Harvard University-led TOHP trial in the United States in the late 1980s and early 1990s. About 4,500 people were divided into groups of subjects who received either general healthy lifestyle advice, or weekly group and individual counselling on how to reduce their sodium intake.
Both sodium consumption and blood pressure fell in the sodium-counselling groups, the researchers found. And then in a later follow-up study, they concluded that those who had received the salt-reduction help were 25 per cent less likely to suffer strokes, heart attacks and other cardiovascular events in the subsequent 10 to 15 years.
Other carefully controlled studies have reached similar conclusions — a straight-line reduction in hypertension as people take in less sodium, said the recent paper by Campbell and colleagues.
One of the first, inadvertent challenges to that understanding came in 2009, when Yusuf and his colleagues decided to look at the issue as part of two large studies they ran, focused mainly on testing blood pressure drugs. About 28,000 people in 40 countries were enrolled in a sidebar sodium study.
Each of the participants — all at risk of cardiovascular disease — had their sodium intake measured by looking at secretions of the mineral in samples of their urine.
What the scientists found jolted them. Instead of that straight-line reduction in heart-and-stroke-related illness as sodium levels fell, the rate of those problems dipped, then actually rose again at estimated sodium intake amounts of lower than three grams a day — making for a J-shaped curve.
In other words, not only did cutting sodium below a certain point not lead to better cardiovascular health, it looked like those lower levels might actually increase the risk of disease.
“We thought ‘That’s peculiar,’” recalls McMaster epidemiology Prof. Andrew Mente, one of the study’s authors. “Then we sat on that data for two years. We did everything we could to make it go away, and we couldn’t make it go away, no matter how you analyze the data.”
They published the results in the prestigious Journal of the American Medical Association in 2011, and the fight was on.
The team followed up with a parallel study of 102,000 subjects from 17 countries in another McMaster-led international research project called PURE.
The results, published in the equally high-profile New England Journal of Medicine, were similar to the earlier ones.
They also argue the earlier evidence, like the TOHP trials, failed to show that reducing sodium to the recommended levels improved health.
For Mente, the takeaway advice is to keep sodium consumption no higher than four or five grams a day, and not worry about cutting it much below three grams.
“The bottom line is, if low sodium is not helpful and may even increase the risk, it’s better to focus on the overall quality of the diet,” he said. “Reduce processed foods and focus on eating more fruits and vegetables and more potassium-containing foods — an all-around wellness diet.”
But critics of the work were quick to dismiss it as poorly conducted, not least because of a crucial, if esoteric, issue: how the levels of sodium intake were measured.
The gold-standard method is to collect all the urine someone produces in a 24-hour period and test for secreted sodium, then repeat the process on non-consecutive days. The McMaster-led team, though, did a single “fasting” or spot sample of urine right after their subjects woke up. Then they used what’s called the Kawasaki formula to essentially extrapolate how much sodium the person consumed over the course of a whole day.
Using the spot-sample method would necessarily distort the results, says the paper last fall critiquing the research, and not just because it paints an inaccurate picture of salt consumption.
That Kawasaki formula incorporates variables like age, weight and sex which themselves are independent predictors of cardiovascular illness, further muddying the results, said the paper.
A 2019 report by the U.S. National Academies of Sciences, Engineering and Medicine came to a similar conclusion, saying the studies’ methods for measuring sodium intake “introduce important biases” that could affect the results.
“It’s tough and it’s tedious so people try to cut a lot of corners,” says Campbell about 24-hour sampling. With a single spot sample “studies are much easier to do, much less complex — and give you the wrong answers.”
Yusuf responds that conducting multiple 24-hour urine testing on a study population of 100,000 or more would be prohibitively expensive, and that the formula, while not perfect, has been shown to be reasonably accurate.
Meanwhile, some studies using the 24-hour method have had similar results, as have several others that employed spot-sampling, noted Mente.
Campbell also questions why the research was given such high-profile treatment. Big name medical journals appear too eager to publish such studies and overlook their alleged flaws, he says, perhaps because the controversial findings create a “man-bites-dog” sort of appeal that draws more readers.
Mente said their sodium studies have been subjected to intense peer review, which at the most prominent journals typically means vetting by half a dozen scientist-reviewers and two statisticians.
Then there is the question of conflict of interest, raised in both the letter to Duclos requesting a federal inquiry and the one to the Canada Council asking it to take back the award it gave Yusuf.
There’s some limited evidence of actual food industry funding in association with the McMaster group. A 2014 conference on nutrition and cardiovascular disease they ran received money from the Campbell Soup Company, ConAgra Foods Inc, Kraft Foods Group and PepsiCo Inc., its agenda indicated.
The PURE study lists about 70 funders, including several major public sector agencies, health charities and drug companies. And it says Brazil’s Unilever Health Institute and the South African Sugar Association gave money to branches of the project in those two countries.
But could there be another, more indirect conflict of interest in their research?
Juliet Guichon, a lawyer and University of Calgary professor of medicine who’s working with Campbell, points to the tens of millions of dollars in funding the McMaster group has received from pharmaceutical companies that produce blood pressure medication.
Yusuf and his colleagues have “consistently failed to acknowledge” money from such sources, said the letter asking that his Killam award be revoked, though at least some of that information is contained in journal papers and other material they’ve produced.
Mente dismisses the notion that funding from makers of blood pressure drugs could bias them against reducing salt consumption — a non-pharmaceutical approach to preventing hypertension and its consequences.
“That is completely far-fetched,” he said. “It’s ridiculous. I won’t even dignify that one.”
Campbell, meanwhile, contends that the sodium debate is not a clash between evenly matched scientific camps — it is “a relatively small group of dissenting scientists (versus) mainstream science.”
Yet those “dissenters” are providing ammunition to food companies loathe to reduce their products’ addictive salt content, he says. The industry is using the work to lobby countries against taking action to cut consumption, said the University of Calgary professor, undermining preventive health care that could save lives and curb spending.
But Yusuf says the science is in flux and their research has helped alter the sodium-hypertension paradigm. The critics are just unwilling to consider that things have changed, he said.
“(Campbell’s) enthusiasm for this as a crusader, you have to admire it,” says Dr. Martin O’Donnell, a professor of medicine at the National University of Ireland Galway and a regular collaborator with the McMaster group. “But at the same time, all scientific debate has to be based on respect, it has to be based on openness. It has to be based on entertaining different viewpoints.”