HRT: Model for dietary salt?
Anti-salt zealots display a religious fervor for their cause, trampling scientists who remind them that actual evidence of a health benefit exists only in the end product of elaborate mathematical models extrapolating only blood pressure effects (and even those are often shrouded in withheld statistics preventing replication). There's an arrogance to their advocacy. And a familiarity.
Investigative science reporter Gary Taubes published the lead story in the New York Times Magazine on September 16, asking "Do We Really Know What Makes Us Healthy?" It's the tragic story of well-intended, plausible advocacy of hormone replacement therapy (HRT) for post-menopausal women. The bright promise, the powerful claims and the glittering possibilities all came crashing down a few years ago when it was found that for many if not most of the target audience, the "cure" was killing far more than it was helping.
Taubes called for more "self-doubt" and recommital to the discipline of scientific investigation, foregoing the passion of the righteous objective for the surer cycle of scientific advance -- proposing hypotheses, testing them to discard most of them and then repeating the cycle to refine those who pass muster.
As he pointed out:
While it is easy to find authority figures in medicine and public health who will argue that today’s version of H.R.T. wisdom is assuredly the correct one, it’s equally easy to find authorities who will say that surely we don’t know. The one thing on which they will all agree is that the kind of experimental trial necessary to determine the truth would be excessively expensive and time-consuming and so will almost assuredly never happen. Meanwhile, the question of how many women may have died prematurely or suffered strokes or breast cancer because they were taking a pill that their physicians had prescribed to protect them against heart disease lingers unanswered. A reasonable estimate would be tens of thousands.
In conclusion, Taubes cautions:
All of this suggests that the best advice is to keep in mind the law of unintended consequences. The reason clinicians test drugs with randomized trials is to establish whether the hoped-for benefits are real and, if so, whether there are unforeseen side effects that may outweigh the benefits. If the implication of an epidemiologist’s study is that some drug or diet will bring us improved prosperity and health, then wonder about the unforeseen consequences. In these cases, it’s never a bad idea to remain skeptical until somebody spends the time and the money to do a randomized trial and, contrary to much of the history of the endeavor to date, fails to refute it.
Epidemiology has its limits, and Taubes explains how epidemiologists moving from infectious diseases a hald century ago to apply the same techniques to prevention of chronic disease have come a cropper:
In the case of H.R.T., as with most issues of diet, lifestyle and disease, the hypotheses begin their transformation into public-health recommendations only after they’ve received the requisite support from a field of research known as epidemiology. This science evolved over the last 250 years to make sense of epidemics — hence the name — and infectious diseases. Since the 1950s, it has been used to identify, or at least to try to identify, the causes of the common chronic diseases that befall us, particularly heart disease and cancer. In the process, the perception of what epidemiologic research can legitimately accomplish — by the public, the press and perhaps by many epidemiologists themselves — may have run far ahead of the reality. The case of hormone-replacement therapy for post-menopausal women is just one of the cautionary tales in the annals of epidemiology. It’s a particularly glaring example of the difficulties of trying to establish reliable knowledge in any scientific field with research tools that themselves may be unreliable.
Advocacy of HRT was based on epidemiology. Again, Taubes:
The dangerous game being played here, as David Sackett, a retired Oxford University epidemiologist, has observed, is in the presumption of preventive medicine. The goal of the endeavor is to tell those of us who are otherwise in fine health how to remain healthy longer. But this advice comes with the expectation that any prescription given — whether diet or drug or a change in lifestyle — will indeed prevent disease rather than be the agent of our disability or untimely death. With that presumption, how unambiguous does the evidence have to be before any advice is offered?The catch with observational studies like the Nurses’ Health Study, no matter how well designed and how many tens of thousands of subjects they might include, is that they have a fundamental limitation. They can distinguish associations between two events — that women who take H.R.T. have less heart disease, for instance, than women who don’t. But they cannot inherently determine causation — the conclusion that one event causes the other; that H.R.T. protects against heart disease. As a result, observational studies can only provide what researchers call hypothesis-generating evidence — what a defense attorney would call circumstantial evidence.
Testing these hypotheses in any definitive way requires a randomized-controlled trial — an experiment, not an observational study — and these clinical trials typically provide the flop to the flip-flop rhythm of medical wisdom. Until August 1998, the faith that H.R.T. prevented heart disease was based primarily on observational evidence, from the Nurses’ Health Study most prominently. Since then, the conventional wisdom has been based on clinical trials — first HERS, which tested H.R.T. against a placebo in 2,700 women with heart disease, and then the Women’s Health Initiative, which tested the therapy against a placebo in 16,500 healthy women. When the Women’s Health Initiative concluded in 2002 that H.R.T. caused far more harm than good, the lesson to be learned, wrote Sackett in The Canadian Medical Association Journal, was about the “disastrous inadequacy of lesser evidence” for shaping medical and public-health policy. The contentious wisdom circa mid-2007 — that estrogen benefits women who begin taking it around the time of menopause but not women who begin substantially later — is an attempt to reconcile the discordance between the observational studies and the experimental ones. And it may be right. It may not. The only way to tell for sure would be to do yet another randomized trial, one that now focused exclusively on women given H.R.T. when they begin their menopause.
And he continued:
In January 2001, the British epidemiologists George Davey Smith and Shah Ebrahim, co-editors of The International Journal of Epidemiology, discussed this issue in an editorial titled “Epidemiology — Is It Time to Call It a Day?” They noted that those few times that a randomized trial had been financed to test a hypothesis supported by results from these large observational studies, the hypothesis either failed the test or, at the very least, the test failed to confirm the hypothesis: antioxidants like vitamins E and C and beta carotene did not prevent heart disease, nor did eating copious fiber protect against colon cancer.
It's a long article and a great read, but the point's been made: We need controlled trials to prevent other HRT tragedies. And a great place to start would be for salt where only observational studies have been done of the projected health outcomes and most of those studies show either no benefit or actual increased risk.
