IJE Advance Access originally published online on February 28, 2005
International Journal of Epidemiology 2005 34(5):972-974; doi:10.1093/ije/dyi016
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Commentary |
Commentary: Possible role of salt intake in the development of essential hypertension
Department of Internal Medicine/Rheumatology Q, Copenhagen University Hospital at Herlev, DK-2730, Herlev, Denmark. E-mail: niagr{at}herlevhosp.kbhamt.dk
Salt is one of the cornerstones on which the mammalian biochemical structure is built. Total exclusion of salt from the diet leads to disaster, namely death.1 Still, salt is considered by some authorities, to be toxic on a level comparable with alcohol and tobacco. Why is salt the only essential component of mammals to have obtained this unattractive status? As of 2004, the history behind this is exactly 100 years old and LK Dahl2 plays an important role in this history. The purpose of the present commentary is to discuss one of Dahl's papers, ‘Possible role of salt intake in the development of essential hypertension’ from 1960. To do this it is important to consider the paper in the historical context in which it was written.
The modern salt saga started in 1904 with a paper by Ambard and Brochard3 who showed an association between salt intake and blood pressure in six patients. On the basis of these observations they created a salt–blood pressure hypothesis. Subsequently in 1907 the results were opposed by Lôwenstein,4 and from then on the salt–blood pressure hypothesis has been the basis for a dispute between supporters of the hypothesis and sceptics. What we can learn from this is that the salt–blood pressure hypothesis and the controversy dates back to the first decade of the previous century, initially based on a few case histories.3,4 To begin with the chloride ion was thought to play an important role, but with the paper by Blum in 19215 the dominant element was gradually concluded to be sodium. At that time the discussion started in the USA with Allan's recommendations of rigid salt restriction for hypertensive patients.6 In the following years Allan's positive results were both confirmed and disproved by several authors, but during the late 1930s the use of salt restriction faded. In 1944 and in the following years the salt controversy was renewed with the introduction of Kempner's rice diet.7,8 Dahl enters the scene around 1950 and until his death in 1975 he was probably the most important contributor to the salt–blood pressure hypothesis. However, before Dahl's entry, in 1949, Chapmann and Gibbons reviewed the first 45 years of the salt controversy in an excellent article1 that can be highly recommended for anyone interested in the field. They reviewed papers by more than 30 authors based on a total of 1573 patients who had been treated with low sodium diet, most of them according to the principles of Allan or Kempner.
Recently the political aspects of the salt controversy were reviewed in Science.8 In this paper 12 touchstones were mentioned, the first one being a paper by Dahl from 1972. This emphasizes the significance of his work.
In the introduction of his 1960 paper Dahl defines his position, namely that salt is deleterious. Salt is compared with fall-out, carcinogens and atherogenic factors, and later in the paper with tobacco, alcohol, and fat. Dahl begins with an argument that the need for salt is lesser than the actual ingestion of salt. This is correct. Most people ingest more salt than needed, but in the western world this could be generalized to all minerals, vitamins, energy sources, and even water. In the statement that primitive populations do well with very small intakes of sodium there is an indication that Nature did not intend man to eat large amounts of salt. However, if this was the case, why did Nature provide man with an excellent apparatus to conserve and secrete sodium (the kidneys and the renin-angiotensin-aldosterone system)? It is as if Nature has foreseen that some people would live in areas with plenty of sodium and others in sodium deficient areas. Moreover, Nature may have foreseen that man would use salt to preserve food in order to avoid food poisoning and that man would create direct aldosterone antagonists (spironolactone), indirect aldosterone antagonists (ACE inhibitors), and natriuretics (diuretics). In the western world an increasing number of patients are admitted to hospitals with hyponatriaemia, a potentially dangerous condition, due to side effects from these treatments, which are given not only for hypertension but to millions of patients with heart failure. Second, Dahl discusses salt intake and concludes that determination of 24 h urine sodium excretion is an excellent measure of sodium intake. Dahl contributed studies to show this, and today this is a well-established fact. Dahl shows that salt intake varies widely between populations and within populations and he argues that even a few grams extra per day leads to a significant increase in the turnover rate of body sodium, which may have physiological implications. I suppose that Dahl implies here that these physiological implications include an increase in blood pressure, but the fact is that there is no scientific proof for that hypothesis. In the next section Dahl deals with salt induced hypertension in animals, especially rats, and the cited studies support the notion that chronic excess salt feeding induces hypertension in a considerable fraction of these animals. However, in 1979 Simpson pointed out that the amount of salt given to the rats in these studies would correspond to about 560 grams per day in a human, i.e. 50 times more than the average intake in the western world.9 Therefore these results probably have no physiological relevance for humans.
In the case of humans, Dahl states that ‘This idea (salt restriction) is so widely accepted and used that dilation would belabour the obvious’. Dahl then goes through a pilot study in which the persons included were divided into three groups according to salt intake during life, low intake, average intake, and high intake. He finds that the higher the salt intake, the higher is the incidence of hypertension. This is followed by a cross-sectional population study confirming a similar association of high salt intake with a high prevalence of hypertension in populations.
Let me focus on some of these statements. The authoritarian argument that ‘dilation would belabour the obvious’ is of course not an argument. From Chapman and Gibbons1 we know that the literature before 1949 is controversial and lacks controlled studies, and the additional references mentioned by Dahl are all uncontrolled observations. Concerning the pilot study, no details are given concerning the measures—if any—that were used to avoid confounding and biases. For instance we do not know whether blood pressure was recorded blindly. Consequently it is impossible to evaluate the results of this study. Concerning the cross-population study, this was retrospective and therefore it was not possible to correct for confounders. Dahl does not even mention that confounders could explain the results. Similar studies, by Gleibermann,10 by our group,11 and Intersalt12 confirm Dahl's results in a design not corrected for confounders. However, confounders were investigated by Intersalt and when a correction for these was introduced the association between blood pressure and salt intake almost disappeared. Furthermore, if four primitive populations were excluded from the analysis, leaving 48 comparable civilized populations, the association was actually reversed. This shows the insufficiency of Dahl's study. Dahl reviews his own papers since 1954. However, it is disappointing that Dahl ignores the fact that debate about the influence of salt started much earlier. Furthermore, it is striking how few of Dahl's references to the salt hypothesis are sceptical. This indicates that Dahl's paper is unbalanced in terms of selection of the literature. As a counterbalance, I therefore find it refreshing at this point to summarize the conclusions of Chapman and Gibbons.1
Chapmann and Gibbons reviewed the period from 1904 to 1949. The results of the reviewed studies varied, but the overall trend was that there was a significant effect of sodium reduction on blood pressure. However, Chapman and Gibbons concluded that there was a universal absence of adequate control studies and a failure to take into consideration the fact that hypertension responds to suggestion and hospital environment alone, regardless of other therapeutic measures. Citing Goldring13 Chapman and Gibbons mention that ‘the better the control observations the less striking are the results.’ On the other hand Chapman and Gibbons also state that ‘it seems idle to insist that all these results can be ignored merely because factors other than dietary restriction may have produced them’. Consequently, Chapman and Gibbons had a balanced view and did not refuse the possibility that sodium reduction could have an effect on blood pressure. They advocated controlled studies, which was a reasonable demand even in 1949. Already in 1898 the later Nobel Prize winner, Fibiger, gave a description of the randomized controlled study, although only in Danish.14 The international breakthrough for the randomized study was in 1948,15 but already in 1945 Fraser published a double-blind randomized controlled study on the effect of gold on rheumatoid arthritis in ‘Annals of the Rheumatic Diseases’. Consequently, sufficient methodological measures were developed to perform properly designed studies on humans.
Altogether, looking at Dahl's work in the present circumstances it is difficult to consider it to be a solid piece of work. However, it is easy to be retrospectively wise on behalf of others. Unfortunately, it is also difficult to accept the work even when taking the time of publication into consideration. History tells us that in 1960 intelligent and critical studies and reviews of the subject had been performed and sufficient scientific methods had been developed to give methodologically a much better and much more critical analysis, than the one Dahl gave us. To be fair, Dahl has shown that 24 h urine excretion of sodium is a reliable measure for sodium intake and through his rat experimental studies he has provided valuable information of the physiological effects of overdosing of salt in salt-sensitive rats. Furthermore, he was the first to associate salt intake and blood pressure between populations and therefore was an important inspiration for the later Intersalt study. Undoubtedly, therefore Dahl has contributed with important and significant results of salt metabolism and physiological effects. However, my conclusion is that Dahl was uncritical of his own results and concluded more than they could bear.
Let me end this commentary by putting Dahl's work into the context of today. Dahl began his contributions to the salt blood pressure conflict at a time when no medical treatment for hypertension existed (around 1950) and he ended his contributions when the era of randomized studies of the effect of sodium reduction began in 1973.16 In 1950 the salt controversy was about the association of salt intake with hypertension. The randomized studies since 1973 have now eliminated this controversy, because supporters and sceptics have, in meta-analyses, agreed that sodium reduction decreases blood pressure by about 4/2 mm Hg in hypertensive persons.17,18 Ironically, in the mean time, we have got so many more efficient medical treatments that the place of sodium reduction in the treatment of hypertension is probably rather marginal. Today we even have a dietary measure that is more efficient and more acceptable for the patients than sodium reduction, namely the intake of fruits and vegetables.19 However, the randomized studies have shown an effect of sodium reduction not only on hypertension, but also of about 1 mm Hg in healthy, normotensive persons.17,18 The new controversy is whether this effect, if applied to the whole population, would have a beneficial effect on the morbidity and mortality of the population and whether this unproven assumption should lead to a general recommendation of sodium reduction in the population.
It is tempting to end this commentary with another provocative citation from Chapman and Gibbons:1 ‘Many (articles) possess historical interest only. Others, while defective in some respects, contain suggestions that have led to later and more valuable work. Still others have had influence out of all proportion to their intrinsic work and are responsible for vast amounts of wasted research endeavour on the part of later investigators’. In that connection, considering that the salt controversy now is dealing with an effect size of about 1 mm Hg, one may ask, has it been worth 100 years of effort?
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1 Chapmann CP, Gibbons TB. The diet and hypertension. A review. Medicine 1949;29:29–69.
2 Dahl LK. Possible role of salt intake in the development of essential hypertension. In: Cottier P, Bock KD (eds). Essential Hypertension—an International Symposium. Berlin: Springer, 1960, pp. 53–65. (Reprinted Int J Epidemiol 2005;34:967–972.)
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17 Cutler JA, Follmann D, Allender PS. Randomized trials of sodium reduction: an overview. Am J Clin Nutr 1997;65(suppl.):643S–51S.
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