I appreciate the opportunity to review and comment on the four responses to my review of sodium and human health. The fair-minded assessment by Drs Freedman and Petitti is most valued, but I must admit to some disappointment at the less supportive reviews registered by Drs MacGregor, and Stamler and Elliott. I will try to briefly clarify the points I tried to make in the original piece.
First of all, I want to emphasize the wide areas of agreement. Sodium intake is related to blood pressure. Meta-analyses of more than 100 randomized clinical trials provide the best estimate of the aggregate effect produced by roughly halving dietary sodium intake, which is in the middle single-digit range for systolic, and the low single digits for diastolic blood pressure more for hypertensive and less for normotensive subjects. But it is also well established that the aggregate changes in blood pressure associated with sodium restriction mask great individual variation. Moreover, reduction in sodium intake activates the renin angiotensin and sympathetic nervous systems, and increases insulin resistance. The human health effect of sodium variation is thus the sum of perturbations of these, and probably other unrecognized surrogate physiological endpoints. This net health impact cannot be determined by extrapolating from effects on selected surrogates, but requires a direct examination of the relation of sodium intake to the quality and duration of human life.
That leads to my second point. For the general population, there are no experimental studies to determine the impact of salt intake on morbidity and mortality. There are four published observational studies, and a fifth unpublished but widely presented observational study, linking a baseline measure of sodium intake with subsequent morbidity and mortality. Two of these show no association of sodium intake to outcome, two show a positive relation of dietary sodium to outcome among the obese minority and no relationship in the normal weight majority. The final study shows increased salt intake to be associated with longer survival. As I see it, this heterogeneity in health associations is the logical consequence of the genetic, behavioural, and environmental variety of humankind, and the well-demonstrated heterogeneity in physiological responses to reduced sodium intake. No doubt, it is this lack of compelling support from available observational studies that has kept any salt hypothesis from submission to an empirical test.
Finally, I tried to assess the role that sodium restriction might play in the management of hypertensive patients. Sodium restriction does lower the pressure of some, but not all hypertensive patients, and like other interventions, sodium restriction affects many non-blood pressure surrogate endpoints. To the disappointment of adherents to evidence-based medicine, there are no randomized studies to assess the net health effect suggested by changes in these surrogate endpoints among hypertensive patients. Indeed, only one observational study addresses the relationship of sodium intake to outcome. In that study of 3000 patients, a strong inverse relation of 24-hour urinary sodium to cardiovascular outcome was found. Because of the potential for confounding, physician scientists are wisely reluctant to draw therapeutic conclusions from that single observational study. Much ink has been spilled debating whether the one existing observed association is what it seems to be. Of course, were we to discount the one available study, data linking salt intake to health outcome would fall to zero! Perhaps it is time to repeat the study, avoiding its weaknesses. In the meantime, my own position is that sodium restriction is one of many interventions that can lower blood pressure. It is a relatively weak and costly intervention but, like others, it does lower the blood pressure of some patients. Based upon my understanding of evidence-based medicine, this approach should be reserved for higher risk patients in whom proven therapies are either inadequate or unacceptable. For this group, it seems likely that if salt restriction lowered pressure, benefit is more likely to result than harm.
Many respected and thoughtful scholars and policy makers would extrapolate from the positive segments in these data, and dismiss those which are at variance with their views. Others feel that it is generally safer to pay attention to all the data, particularly when they are inconsistent with preconceived beliefs. They would argue that change in the diets of millions of healthy people or hypertensive patients should be based on empirical evidence that the net result of such a change would be positive.
Where should we go from here? We could continue to dissect the few shards of data available to support or refute particular views, but I think opinion, no matter how passionately or widely espoused, is a poor substitute for solid scientific evidence when making medical or public health recommendations.
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