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    7 views9 pages

    Science Political Science of Salt1

    Uploaded by

    Rc Sete
    NaCl

    Copyright:

    © All Rights Reserved
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    DEES Three decades of controversy over the putat benefits of salt reduction show how the demands of ‘good science clash with the pressures of public health policy The (Political) Science of Salt Science ... warns me to be careful how adopt a view which jumps with my precon- ceptions, and t0 require stronger evidence {for such belief than for one to which I was previously hostile. My business is 10 teach ‘my aspirations to conform themselves 10 fact, not to try and make facts harmon ‘with my aspirations ~Thomas Huxley, 1860 In an era when dietary advice is dispensed freely by virtually everyone from public health officials to personal trainers, well- ‘meaning relatives, and strangers on check-out lines, one recommendation has rung through 3 decades with the indisputable force of ‘gospel: Eat less salt and you will lower your blood pressure and live a longer, healthier life. This has been the message promoted by both the National Heart, Lung, and Blood In- stitute (NHLBI and the National High Blood Pressure Education Program (NHBPEP), a coalition of 36 medical organizations and six federal agencies. Everyone, not just the tens ‘of millions of Americans who sul fom hy- pertension, could reduce their risk of heart disease and stroke by eating less salt, The of- ficial guidelines recommend a daily al- Towance of 6 grams (2400 milligrams of sodium), which is 4 grams less than our cut- rent average. This “modest reduction,” says NHBPEP director Ed Roccella, “ean shift some arterial pressures down and prevent some strokes." Raccela’s message is clear: “AIL T'm trying to do is save some lives.” ‘So what's the problem? For starters, salt is a primary determinant of taste in food—fa, of course, isthe other— and 80% of the salt we con- sume comes from pro- cessed fonds, making it difficult to avoid ‘Then there's the kicker: While the government has been denouncing salt as a health hazard for decades, no mount of scientific effort has been able to dlspense with the suspicions that itis not. In- deed the controversy over the benefits, if any, of salt reduction now constitutes one of the longest running, most vitriolic, and surreal disputes in all of medicine. ‘On the one side are those experts—pri= marily physicians tumed epidemiologists, and administrators such as Roscella and Claude enfant, head of NHLBI—who insist tha the ‘evidence that sat raises blood pressure is feetivelyirefutable. They have an obligation, they say, to push for universal salt reduction, because people are dying and will continue to die if they wait for further research to bring sciemtfic certainty. On the other side are those researchers primarily physicians turned epidemiologists, including former presidents of the American Heart Associa- tion, the American Society of Hypertension, and the European and international societies ‘of hypertension—who argue that the data supporting universal salt reduction have never been compelling, nor has it ever been demon- strated that such a program would not have _unforescen negative side effects. This was the verdict, for instance, ofa review published last May in the Jounal of the American Medical Association (JAMA). University of ‘Copenhagen researchers analyzed 114 ran- The salt controversy is the “number one perfect example domized trials of sodium reduction, conclud= ing that the benefit for hypertensives was si nificantly smaller than could be achieved by antihypertensive drugs, and that a “measur- able” benefit in individuals with normal blood pressure (normotensves) of even a single mil= limeter of mercury could only be achieved with an “extreme” reduction in sat intake “You can say without any shadow ofa doubt” says Drummond Rennie, aJMA editor and a physiologist at the University of California (UC), San Francisco, “thatthe [NHLBI] has made a commitment to salt education that ‘goes way beyond the scienic facts” ‘AL its core, the salt controversy is a philosophical clash between the require ‘ments of public health policy and the quirements of good science, between the need to act and the institutionalized skept cism required to develop a body of reliable Knowledge. This is the conflict that fuels ‘many of today’s public health controversies: ‘We're all being pushed by people who say, "Give me the simple answer. Is ito isnt?" says Bill Harlan, director of the office of disease prevention atthe National Institutes ‘of Health (NIH). “They don’t want the an- sswer after we finish a study in S years. They ‘want it now. No equivoeation ... [And so] ‘we constantly get pushed into positions we ‘may not want to be in and cannot justify scientifically” ‘The dispute over salt, however, is an id- josyneratic one, remarkable in several funda- mental aspects. Foremost, many who advo- cate salt reduction insist publicly thatthe ‘controversy is a) either nonexistent, or b) due solely tothe influence of the salt lobby and its paid consultant- scientists, Jeremiah Stamler, for instance, a cardiolo- ‘ist at Northwest- ‘ern University Medical of why science is a destabilizing force in public policy. ford Miller PHOTOGRAPHY BY ANN ELLIOTT CUTTING School in Chicago who has led the charge ‘yainst salt for 2 decades, insists thatthe con- tronersy has “no genuine scientific basis in e- ‘roducible fact” He attributes the appearance ‘of controversy tothe orchestrated resistance of the food processing industry, which be likens to the tobacco industry in the fight over cigarettes, alvays eager to obfuscate the facts. “My considerable experience indicates that ‘there is no scientific interest onthe part of any ‘of these people to tel the truth” he says. While Stamler’ position may seem ex- treme, itis shared by administrators atthe \NHBPEP and the NHLBI, which funds all relevant research in this county, Jeff Cutler, director of the division of clinical applica tions and interventions at NIH and an advo- cate of salt restriction for over a decade, told ‘Science that even to publish an article such as this one acknowledging the existence of the controversy is to play into the hands of the salt lobby. “As long as there are things in the media that say the salt controversy con- tinues,” Cutler says, “they win.” Roccella concurs: To publicize the controversy, he tld Science, serves only to undermine the public health ofthe nation ‘Afr interviews with some 80 researchers, clinicians, and administrators throughout the ‘world, however, it is safe to say tha if ever there were a controversy over the interpret tion of scientific data, this is it Infact, the salt controversy may be what Sanford Miller calls the “number one perfect example of why s ence isa destabilizing force in publ policy’ ‘Now a dean at the University of Texas Health Sciences Center, Miller helped shape salt pol fey 20 years ago as director of the Center for Food Safety and Applied Nutrition at the Food and Drug Administration. Then, he sys, the data were bad, but they arguably support- ed the benefits of salt reduction. Now, both the data and the science are much improved, but they no longer provide forceful support forthe recommendations That raises the Second noteworthy aspect of the controversy: After decades of intensive research, the apparent benefits of avoiding salt have only diminished. This suggests either that the true benefit has now been revealed and is indeed small, or that itis nonexistent, and re- searchers believing they have detected such benefits have been deluded by the confound ing inuences of other variables. (These might include genetic variability; socioeconomic st tus, obesity; level of physical exercise; intake of alcoho, fruits and vegetables, or dry prod ucts, or any numberof other factors.) The controversy itself remains potent be- ‘cause even a small benefit—one clinically meaningless to any single patient—might have a major public health impact. This is @ ‘principal tenet of public health: Small effects ‘can have important consequences over entire populations. IFby eating less salt, the world’s wwrwsclencemagorg SCIENCE VOL281 population reduced its average blood pres- sure by a single millimeter of mercury, says Oxford University epidemiologist Richard Peto, that would prevent several hundred ‘thousand deaths a year: “It would do more for worldwide desihs than the abolition of breast cancer” But even that presupposes the L-millimeter drop can be achieved by avoiding salt, “We have to be sure that I- oF 2-millimeter effect is real,” says John Swales, former director of research and de- velopment for Britain's National Health Ser- vice anda clinician at the Leicester Royal n- firmary. “And we have to be sure we won't have equal and opposite harmful effets” Decades have passed without a resolution because the epidemiologic tools are inca- pable of distinguishing a small benefit from. 1 benefit or even fom a small adverse ef tonal Center for Health Statistics. Among their criticisms was that MeCarron and col- Teagues had not “attemptfed) to square their ‘conclusions with the abundance of population based and experimental data suggesting that dietary sodium indeed plays an important role in hypertension’ At the time of the leer, however, Lenfant’s NHLBI was about t0 fund perhaps the largest international study ever done, known as Intesalt, precisely to de termine whether salt did play such a role ‘And even Stamler, the motivating force be- hhnd Intersalt, was describing the literature on salt and blood pressure atthe time as “replete ‘with inconsistent and contradictory reports” One-sided interpretations of the data hhave always been endemic to the controver- sy. As early as 1979, for instance, Olaf Simpson, a clinician at New Zealand's Uni- versity of Otago Medical School, de- scribed it as “a si- tuation where the most slender piece ‘You can say without {hice nie any shadow of adoubt °.!%_ ssi Boot that the [NHLBI]has ooo tine ink made acommitment “file ont to salt education that Paine! awiy by one means or another” “alll'm goes way beyond the Urn of Gin. tryingto scientific facts.” Waals in A “Bing Crosby ape doissave —— _prummond Renn proach epidemic some ine nor live cent the posi- ‘ect, Tis has led t a literature so enormous and conflicting that itis easy to amass a body of evidence—what Stamler calls a “totality of ddata"—that appears to support a particular convietion definitively, unless one is aware of the other totality of data tha doesnt Over the years, advocates of salt reduction have often wielded variations on the “tality of data” defense to reject any finding that doesn fit the orthodox wisdom. In 1984, for instance, David McCarron and colleagues from the Oregon Health Sciences University in Portland published in Science an analysis of a national health and mutition database ‘suggesting that salt was harmless. They were taken to task in these pages by Sanford Miller, Claude Lenfant, director of NHLBI, ‘and Manning Feinleb, then head of the Na: tive, eliminate the negative” Bing Cros- by epidemiology al lows researchers to find the effet they te looking for in a ‘swamp of contradictory data but does litle © establish whether itis real ‘This situation is exacerbated by a remark- able inability of researchers inthis polarized field to agree on whether any particular study is believable, Instead, tis common for stud- ies to be considered reliable because they get the desired result In 1991, for instance, the British Medical Journal (BM) published a [M.page, three-part “meta-analysis” by epi demiologists Malcolm Law, Christopher Frost, and Nicholas Wald of the Medical Col- lege of St, Bartholomew's Hospital in Lon- don, Theit conclusion: The salt-blood pres- sure association was “substantially larger” than previously appreciated. That same year, Swales deconstructed the analysis, which he describes as “deeply flawed,” at the annual ‘4AUGUST 1998 99 ‘TOUCHSTONES OF THE SALT DEBATE Dahl eal, 1972. Clinica, ecological, and rat studies supporting salt-blod pressre lnk Gleibermann et al, 1973. Review of 27 eco- logi stusie suggests a direct ner rela- tionship between salt and blood pressure Cooper e at, 1979. Intrapoplation study of several hundred schooeilren su fests not wholly negtive” relationship Eten salt and Bld pressure MeCarron et al, 1984. Analysis ofthe [National Health and Nutrition Examine tion Survey database suggests that salt is harmless and that calcium and potassium protect against hypertension, Smith ef a, 1988 (Scottish Heart Health Study). Study of 7300 Scottish men finds no relationship between salt intake and blood pressure. Interslt, 1988. study of 52 200-person populations shows weak or no relation- hip between salt and bloodpressure but infers a relationship between salt and the Fis in bloodpressure with age. Intersalt Revisited, 1996, statistical reanal~ ‘is ofthe orginal intersale data now finds Strong, consistent positive association Be- ‘ween salt and blood pressure. Cutler et al, 1991. Meta-analysis of 27 clinica vials finds that salt reduction lowers blood pressure in both hyperten- slves and normatensives 1991, Review of 24 ecologic studies, 14 intrapopulation studies, and 7B clinical trials finds that salt-blood pressure link s "substantially larger” than generally appreciated and increases with age, Midgley etal, 1986. Meta-analysis of $6 linia trials concludes that benefit from Salt eduction Is small and doesnot sup- port current dietary recommendations. Meta-analysis of 32 Benefit of salt reducto nd does support current deta dations. ‘Tas of Hypertension Prevention Collab- orative Research Group, 1997 (TOHP I) {linica rial in 2400 subjects Indicates that long-term reductions in salt intake ‘are ard to maintain and result in ttle or no reduction in Blood pressure. Appel et al 1957 (DASH). Cia val of 258 people shows hat dary factors other ton sod have nh greater ‘econ Hood presi. Croudal et al, 1998, Meta-analysis of 14 Sinead agi ecto s goa ‘ecommendaign to rede sle inte. ‘AUGUST 1998 VoL 281 News Focus ‘meeting of the European Society of Hyper- tension in Milan, “There was not a single person inthe room who fet the [4] analy sis was worth anything after that,” says li cian Lennart Hansson of the University of Uppsala in Sweden, who attended the meet- ing and isa former president of both the i ‘temational and European societies of hyper- tension, Swales’ critique was then published in the Jowrnal of Hypertension Just 2 years later, however, the NHBPEP released a landmark report on the primary prevention of hypertension, in which the government first recommended universal salt reduction. The BM meta-analysis was cited repeatedly as “compelling evidence of the value of reducing sodium intake.” This spring, however, it was still possible to get opinions about the BM review from equally respected researchers ranging from “reads like @ New Yorker comedy piece” and the “worst example of a meta-analysis in print by a long shot” to “competentiy done and competently analyzed and interpreted” and ‘a seminal paper inthe field crystallizing a debate The case against salt begins with physio- logical plausibility. Eat more salt, and your body will maintain its sodium concentra- tion by retaining more water. “If you go on salt binge,” says Harvard Medical School nephrologist Frank Epstein, “you will e~ tain salt and with it a proportionate amount of water until our kidneys respond and ex- crete more salt. In most people, you will detect a slight increase in blood pressure when body fluids are swollen like this, al- though there is a very broad spectrum of responses, Behind this spectrum is « homeostatic mechanism that has been compared to a Russian novel in its complexity. The east of characters includes some 50 different nutri- ents, growth factors, and hormones. Sodium, for instance, is important for maintaining ‘blood volume; potassium for vasodilation or constriction; and calcium for vascular smooth muscle tone, Inerease your caloric intake, and your sympathetic nervous system. responds to constrict your blood vessels, thus raising your blood pressure. Decrease yout calories, and your blood pressure falls. ‘To make matters still more complicated, the interplay ofthese variables differs with age, sex, and even race. Most researchers believe that a condition known as salt sensitivity ‘explains why the blood pressure of some in dividuals rises with increased salt but not ‘others, but even that is controversial, says Harlan. No diagnostic test exists for salt sensitivity other than giving someone salt and seeing what happens, which still won't predict whether the sensitivity i lifelong or wansitory. Despite this complesity, most re- searchers stil belive it makes physiological sense that populations with highsalt diets ‘would have more individuals with high ‘ood pressure than those with lw sat diets, and that lowering salt intake would lower blood pressure. By the 1970s, when the government began recommending salt reduction to teat hyper- tension—defined as systolic Blood pressure higher than 140 mmiig and diastolic higher than 90 mig (140/90 mmlg)—the physi ological plausibility ad been supplemented by a grab bag of not particulary definitive studies and clinical lore. In the 1940s, for instance, Duke Univesity clinician Wallace Kempner demonstrated that he could sue= cessflly teat hypertensive patients with a low-salt, rice-and-peaches diet. For years Kempner regime was the only nonsusi= cal treaiment for severe hypertension, a fact that may have done more than anything to convince an enti generation of clinicians of the valve of salt reduction. Ia a seminal 1972 paper, Lewis Dakl, a physician at Brookhaven National Laberatory in Upton, New York, and the primary champion of salt reduction inthis country until his death in 1975, claimed it was proven that alow salt diet reduced blood pressure in byperten- sives. When it didn't, he said, that only proved thatthe patent had fallen of the dit, all protestation tothe contrary, notwith standing” Whether it was low sat that ex plained the dit’s effect is stil debatable, however. Kempner regimen was also ex: ‘raordinaily lw in calories and fat and high in potassium, factors that themselves are now known to fower blood pressure Dall furthered the case fora salt-blood pressue link by breeding a stain of salt Sensitive hypertensive rats, Researches still cit his work as compelling evidence forthe role of salt in human hypertension, As Simp- son pointed out in 1979, however, Dahl’ rats became hypertensive only if fed an amount of salt equivalent to more than S00 grams a day for an adult hurnan—*probably outside the area of relevane,” Simpson noted. Late= ly, researchers have been touting a 1995 study of chimps fed a high-salt diet. But Harlan nots that “i's unlikely” that any ex= isting animal models of hypertension are particularly relevant humans. Throughout the carly years ofthe contro- very, the most compelling evidence against salt came from a type of epidemiologic study known as an “ecologic” study, in which researchers compared the salt intake of indigenous populations—tne Yanomamo Indians of Brazil, for instance—that had lit- tle oF no hypertension and cardiovascular disease to that of industrialized societies. In- evitably the indigenous populations ate litle or no salt; the industalzed societies ate a Jot. While the Yanomamo ate less than a SCIENCE wwwsciencemag.org ‘gram of salt daily, for instance, the northern Japanese ate 20 to 30 grams—the highest ‘salt intake in the world—and had the high- cst stroke rates. Such findings were rein- foreed by migration studies, in which re- searchers tracked down members of low-salt ‘communities who had moved to industial- ized areas only to see both their salt intake and blood pressure rise. “The findings led researchers to postulate ‘an intuitive Darwinian argument forsale f= duction: Humans evolved in an environment ‘where salt was scarce, and so those who sur- vived were those best adapted to retaining salt. This trait, so the argument goes, would hhave-been preserved even though we now live in an environment of salt abundance. By this logic, the appropriate intake of salt is that of the primitive societies—a few ‘grams a day—and all industrialized soci- ties eat far too much and pay it for it in heart disease and stroke ‘The eatch to this accumulation of data and hypotheses was that it only included half the data, The other half was the half that didn’ fit—in particular, data from the ep demiologie studies known as intapopulation studies. These compared salt intake and blood pressure in individuals within a popu- Jation—aales in Chicago, for instance—and invariably found no evidence that those who ate a lot of salt had higher blood pressure than those who ate litle. Among the inra- population studies that came up negative were an analysis of 20,000 Americans con- ducted by the National Center for Health Statistics around 1980, Neither kind of study was capable of giv ing a definitive answer, however. The eco- logie studies were certainly the least sound scientifically, and epidemiologists today put litle stock in them. The potentially fatal flaw in ecologic studies is always the num- ‘oer of variables other than the one at issue ‘that might differ between the populations and explain the relevant effect. Populations that eat litle salt for instance, also consume fewer calories; eat more fruits, vegetables, and dairy products; are leaner and more physically active; drink less alcohol; and are less industrialized, Any one ofthese differ= fences or some combination of them might be responsible forthe lower blood pressure Indigenous people also tend to die young, from infectious diseases or trauma, notes Epstein, while industrialized societies live Jong enough to die of heart disease ‘Both ecologic and intrapopulation stud- {es also suffer from the remarkable difficul- ty of accurately assessing average blood pressure—which can vary greatly ftom day to day-—or a lifetime intake of salt, Most of the early ecologic studies based their as- sessments of salt intake on guesses rather than measurements, In 1973, when Univer= ‘wormsciencemagorg SCIENCE VOL281 News Focus sity of Michigan anthropologist Lillian Gleiberman published whats still consid- ‘ered a seminal paper linking salt and blood pressure, she based her conclusions on 27 ‘ecologic studies, only 11 of which actually ‘tied to measure sodium intake. A 24-hour collection of urine is considered to be the best assessment of salt intake, because we duickly excrete in our urine ail the salt we ‘consume. But even that will only reflect the salt intake of those 24 hours, not necessari- ly of an entire month, year, or lifetime. You nced at least five to 10 measures of sodium in urine collected on different days to get a measure of habitual intake.” says Daan Kromhout, a nutritional epidemiolo- sist at the National Institute of Publi orker comedy _ the “worst example of a meta-analysis in print by Health lands, “You can't do that in an epidemiolog- ie field situation.” ‘To researchers who accept the salt-blood pressure hypothesis, these measurement problems served to explain why intrapopu- lation studies wouldn't see an association even if one existed. Quite simply, the link between salt and blood pressure, however potent, would likely be washed out by the ‘measurement errors. Moreover, ay’ experi= ‘ment large enough to have the statistical power to overcome these errors would be prohibitively expensive. In the early 1980s, London School of ‘Tropical Medicine and Hygiene epidemi- ologist Geoffrey Rose suggested another reason why the intrapopulation studies ‘might fail to detect benefits of salt reduc tion that could still have a significant pub- vaaucust long shot” to lic health impact. Rose speculated that if the entire developed world consumed too much salt, as ecologic studies suggested, then epidemiology would never be able 10 Tink salt to hypertension, regardless of how ‘causal the relationship. Imagine, he wrote, if everyone smoked a pack of cigarettes dailys then any intrapopulation study “would lead us fo conclude that lung can ‘cer was a genetic disease... since if every ‘one is exposed to the necessary agent, then the distribution of cases is wholly deter- ‘mined by individual susceptibility.” Thus, as with salt and high blood pressure, the clues would have to be “sought from dif- ferences between populations or from changes within populations over time.” By the same logic, cutting salt con- sumption a small amount might have litle effect on a single indi- vidual—just as going from 20 cigarettes to 19 would—but a :major impact on mortality across ‘an entire population, Although Rose's proposition ‘made intuitive sens, it stil rested ‘on the unproven conjecture that avoiding salt could reduce blood pressure, conjecture that was be- ginning to seem extraordinarily resistant to any findings that might negate it. In 1979, for in- stance, Stamler and his North: western colleagues tested the hy- pothesis in an intrapopulation study of Chicago schoolehildren, ‘They compared blood pressure in 72 children to salt intake, estimated from seven consecutive 24-hour urine samples, enough to reliably reflect habitual sodium intake. ‘They reported a “clear-cut” rela- tionship between sodium and blood pressure in the children but then tried twice to reproduce the result and failed twice, “A variety of potential explanations of this phenomenon could be advanced” the authors wrote, one of which was the obvi ‘ous: “No relationship in fact exists between sodium and [blood pressure...” They then listed five reasons why they might have ‘missed the expected relationship—insensi- tive measurement techniques, for instance, or genetic variability obscuring the role of sodium, or the possibilty that “the true re lationship is not yet evident in children.” [Because the first of the three studies was positive, Stamler and his colleagues con-

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