Sunday, 11 September 2016

Disproving the cholesterol theory

Researchers are beginning to uncover data hidden for 40 years, and proving all along that the high-fats and cholesterol theory of heart disease was wrong.

There's a joke that used to do the rounds of newspaper offices: don't let the facts spoil the story. Medicine seems to have its equivalent version, with inconvenient truths being buried to safeguard a cherished theory.

Take, for instance, the idea that the fats we eat from butter, dairy and meat raise levels of cholesterol—especially the artery-clogging LDL (low-density lipoprotein) 'bad'sort—which in turn causes heart disease. It's an idea that gained traction in the 1960s and launched the billion-dollar statin drug industry, and the even more lucrative market of low-fat foods and diet drinks.

But a team of researchers from America's National Institutes of Health (NIH) has been uncovering data from old research projects—stored away in boxes and never published—which would have established that the cholesterol theory was wrong.

Not only has the cholesterol theory never been proven (see Where's the evidence? below), but scientists were deliberately hiding the data that demonstrated it was false—and did so for years.
The investigation was sparked by a discovery made by one of the NIH team members, Dr Robert Frantz, a cardiologist at the Mayo Clinic. Frantz had uncovered a box of research papers in the basement of the home of his father, Dr Ivan Frantz, who died in 2009.

Frantz's father had also been a medical researcher and had headed up the Minnesota Coronary Experiment, which ran from 1968 to 1973,thebiggest-ever study into diet, cholesterol and heart disease. The experiment involved more than 9,000 patients recruited at six mental hospitals and a state-run nursing home in Minnesota, and it set out to demonstrate that fats in our food cause heart disease.

Half the patients were fed a high-fat diet, including meat and dairy, while the rest switched to a'healthier' diet of vegetable oils, high in linoleic acid, which replaced the saturated fats. Just as Frantz and his team expected, the patients on the healthier diet saw their cholesterol levels fall—but their chances of a fatal heart attack also rose.

Buried evidence
Although it was the largest trial into cholesterol ever undertaken, it was not published until 1989—but with all the 'difficult' data and confounding results left out! That's what had been gathering dust in Frantz's basement and stayed there until discovered by his son. Robert Frantz sent the box to Chris Ramsden, a medical investigator at the US NIH. For Ramsden, this must have felt like deja vu: he had only just finished analyzing another set of data that had also never seen the light of day. That had been compiled by researchers for the Sydney Diet Heart Study (SDHS), and they had found the self-same thing that Ivan Frantz and his team found: people who eat a healthy diet of vegetable oils were seeing their cholesterol levels fall, but their chances of heart disease and death rose.

The SDHS had been a much smaller trial, involving just 458 men recently diagnosed with heart disease. For seven years, the men ate a diet of saturated fats or switched to one that was high in omega-6 linoleic acid, such as from safflower oil and polyunsaturated margarine, one of the new low-fat products on the shelves when the study started in 1966. Although the Sydney researchers reported that more men on the healthy diet had died, they didn't mention that the cause was heart diseased
Ramsden and his team published their reanalysis of the Sydney study in 2013, which put the record straight: more of those on the healthy diet had died of coronary heart disease and cardiovascular disease. Increasing the amount of linoleic acid we eat might even be adding to the risk of heart disease, they concluded.

Facing the fats
Ramsden was trying to make sense of these data, which flew in the face of the standard dietary advice for the past 40 years or more. Even as recently as 2009, the American Heart Association was reaffirming its advice that a diet low in saturated fats and moderately high in linoleic acid and other omega-6 unsaturated fats was good for the heart. But it's not that simple: when it comes to omega-6 linoleic acid, you can have too much of a good thing. As well as in the vegetable oils used in trials, linoleic acid is also found in nuts and seeds—and processed foods like ready-made chicken meals, salad dressings, potato chips (crisps), pizza, bread and pasta dishes. Most processed foods are made with vegetable oils, and too much linoleic acid becomes harmful. Also, as Ramsden concluded after sifting through data from four major trials, the health benefits due to omega-3 fatty acids—found in fish and certain plant-based foods—were being wrongly attributed to omega-6 fatty acids.

So here they were again, rewriting the conclusions of another research paper. "Altogether, this research leads us to conclude that incomplete publication of important data has contributed to the over-estimation of benefits, and the under-estimation of potential risks, of replacing saturated fat with vegetable oils rich in linoleic acid," said one of Ramsden's researchers, Daisy Zamora, at the University of North Carolina, 291:2536-45 JAMA.1987; 257:2176-80 after the publication of the revised Minnesota study.

But why hadn't the original data been published? Conspiracy theorists reckoned that the older Frantz had been leant on at the very highest levels, whereas others thought the editors of medical journals simply didn't want to publish heretical data. Zamora thinks this was the fate of the Minnesota study. "It could be that they tried to publish all of their results, but had a hard time getting them published," she said. Frantz felt it could have been more a case of self-censorship; his father just couldn't believe the data in front of him. "When it turned out that it didn't reduce risk, it was quite puzzling. And since it was effective in lowering cholesterol, it was weird," he said, guessing at his father's reactions.2
It would certainly have been weird for Frantz father), who had completely bought into the fats-cholesterol-heart disease model. One of his friends at the University of Minnesota was Ancel Keys who, almost single-handedly, pioneered the cholesterol theory. Keys was also a co-author of the Minnesota study, and had announced the launch of the largest-ever study into his theory just before it kicked off. "My father definitely believed in reducing saturated fats, and I grew up that way. We followed a relatively low-fat diet at home, and on Sundays or special occasions we'd have bacon and eggs," said Frantz (son). The older Frantz said as much to medical researcher Gary Taubes two years before his death. He told Taubes the data had been deliberately hidden because "we were just disappointed in the way it came out" Not wishing to disprove the cholesterol theory or upset his best friend, Frantz s father hid the truth for 40 years in his basement. He didn't want the facts to spoil a good theory.

The association between a high-fat diet, cholesterol and heart disease has never been proven.

Where's the evidence?
For a theory that has made billions for the drug and food industries, the association between a high-fat diet, cholesterol and heart disease has never been proven. The US Surgeon General's Office employed four project officers for 11 years to produce a definitive report on the connection between fats and heart disease. In 1999, the Office shut the project down, unable to find any evidence to support the theory. Afterwards, project leader Bill Harlan said, "The report was initiated with a preconceived opinion of the conclusions", and concluded that the science behind the theory just wasn't there.1

The other part of the theory—that cholesterol causes heart disease-has also never been definitively established. Even the prestigious Framingham study, which has tracked the heart health of that small town in Massachusetts since 1948, concluded that high cholesterol levels did not predict fatal heart attacks.

In fact, the researchers found quite the opposite: people with low cholesterol levels were more likely to die of heart disease.2

One of the theory's sternest critics has been Danish researcher Dr Uffe Ravnskov, who heads up The international Network of Cholesterol Sceptics (THINCS). He says that all cholesterol—including HDL and the so-called 'bad' LDL—are vital for our health. As we age, LDL cholesterol is important for maintaining brain health, he says.

So if the cholesterol theory is wrong, what is causing heart disease, still the number-one killer in the West? During the 1950s, when Ancel Keys, a researcher at the University of Minnesota, was laying the blame at the door of a high-fat diet, other scientists were suspecting it was more to do with sugar, which was just starting to appear in processed foods in post-war America. Sugar could be one trigger of inflammation, which scientists are now beginning to quietly accept has a much closer association than previously thought with heart disease and atherosclerosis, where arterial walls become rigid with plaque. One study found that inflammation is an important indicator of coronary heart disease (CHD). They studied 506 men who had suffered a heart attack and compared them with 1,025 heart-healthy men, and found that those with the highest levels of C-reactive protein in their
blood, an indicator of inflammation, were also twice as likely to have CHD.

But inflammation isn't a cause: it's the body's immune response to stress, infection, a bad diet and environmental pollutants. And cholesterol, some believe, is playing a positive role in all of this. Cholesterol, and LDL in particular, is trying to repair inflamed arteries—so attempts to reduce cholesterol levels, such as through a low-fat diet or lipid-lowering drugs, can actually increase our risk of dying from heart disease, just as the scientists who suppressed their own data discovered (see main story above). Having low cholesterol levels isn't bad only for the heart, but also for cancer patients— especially those with gastrointestinal or multiple myeloma cancers, who tend to be low in LDL cholesterol— and older people, who tend to live longer the higher their cholesterol count.

  1. Arteriosclerosis, 1989; 9:129-35
  2. Adv ExpMed Biol, 1978; 109:317-30
  3. BMJ,2013;346:e8707
  4. WorldRevNutrDiet,2011;102:30-43
  5. BMJ, 2016; 353 :i1246
  6. The New York Times,13April2016; http://well.
  7. TaubesG. Good calories bad calories. New York: Anchor Books, 2008
Published in What doctors done tell you magazine. July 2016