NDT Advance Access originally published online on December 29, 2005
Nephrology Dialysis Transplantation 2006 21(8):2052-2056; doi:10.1093/ndt/gfi256
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Salt—friend or foe?
Ruperto Carola University, Heidelberg, Germany
Correspondence and offprint requests to: Eberhard Ritz MD, Ruperto Carola University, Nierenzentrum, Im Neuenheimer Feld 162, D-60126 Heidelberg, Germany. Email: Prof.E.Ritz{at}t-online.de
Keywords: hypertension; oxidative stress; progression; renal disease; salt; sodium
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Introduction—the history of salt |
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Introduction--the history of...
Benefits vs harmWhy is the issue of potential benefit of or damage from salt currently so controversial?
It is rewarding to go beyond medicine and take note of the arguments of the historian Bergier [1]. He argued that salt was an extremely precious item in the distant past and had strong symbolic connotations, both positive and negative. Positive connotations include the fact that this white substance was a symbol of the immaculate, incorruptible, imperishable, as reflected by the Arabian proverb: ‘salt is not worm-eaten’. It was also an emblem of immortality and a symbol of immutable loyalty. This is reflected for instance by the act of sharing bread and salt with a guest—still practised in Slavic countries. The bible tells us that salt was used in the rites of ratifying contracts and sealing covenant as indicated by quotations such as ‘It is a covenant of salt forever, before the Lord’ (Numbers 18; 19) or ‘the Lord God of Israel gave the kingdom of Israel to David forever, to him and to his sons by a covenant of salt’ (Chronicles 13;15).
Salt was also felt to promote health. Today very few people realize that in Latin the words for health and healthy, salus and salubris, were derived from sal, i.e. from salt. When Frenchmen greet each other saying ‘salut’, very few people realize that they are actually referring to salt [2,3].
Salt was a precious commodity, and many words in our languages can be traced back to salt. The payments for soldiers were not coins, but a certain amount of salt, the salarium, which is still today at the root of the words salary in English and salaire in French. The salarium for soldiers is also at the origin of the modern words sold and soldier.
The economic value of salt is also reflected by the fact that many cities are named after salt. When eating a sandwich, few are aware of the fact that the ending ‘wich’ denotes that in the past salt had been produced in a saltern in this specific village. The Celtic syllable ‘hal’ (for salt) is still found in city names such as Hall/Tirol, Halle a. d. Saale. The German word ‘Salz’ or English ‘salt’ is found in village names such as Salzburg, Langensalza and Saltcotes.
Salt was extremely expensive. It cost the consumer 20 times more than its production cost. In France, one-eighth of the income of a peasant family was spent on salt: first because of the heavy salt tax, the gabelle; secondly because 9 kg per head of this expensive salt, called ‘sel de devoir’, had to be bought from Royal stores. Smuggling of salt was the answer. To fight salt smuggling, an extra police force, les gabelous, was created which even fought military actions and was allowed to search private property for hidden salt. It was notorious for molesting women who—on the other hand—used to hide smuggled salt in their underwear. It is little known today that the salt tax was one major reason for the French revolution. The oppressive nature of the tax is reflected by the fact that in the last year before the French revolution, 3500 citizens were sentenced to death or the galleys for salt smuggling [4].
According to Bergier [1], this heavy burden of the past underlies some of the extremely irrational and acrimonious contemporaneous discussions on whether salt is detrimental or beneficial to health, although certainly interventions of the food industry can also not be discounted.
Historically, the use of added dietary salt is very recent. Whereas life originated several billion years ago, salt came into human use only several millennia ago. Hunters and gatherers had consumed <1 g/day, as do still some tribes living under palaeolithic conditions such as the famous Brazilian Yanomamö stoneage hunters living on <3 g of salt per day.
After the introduction of agriculture, salt consumption increased, but even then salt consumption was initially still relatively low.
What were the levels of salt consumption in the more recent past? According to Plinius and Columella, Roman cuisine provided on average 25 g of salt per day. Because of the taxation by the gabelle, excellent records are available for 18th century France, indicating that it was then <20 g/day. Nils Alwall reported that in the 16th century, the daily consumption in Sweden was 100 g/day—mainly due to the fact that during much of the year heavily salted fish was the only food available.
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Benefits vs harm |
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Today there is an ongoing discussion about whether the currently high salt intake in the range of 10–15 g/day in Western societies is innocuous or detrimental.
The notion that too much salt is detrimental has a long history. In the writings of the famous Yellow Emperor, the wise ancient Chinese had stated with sound scepticism 3000 years before Christ: ‘If too much salt is added to food, the pulse hardens, tears make their appearance and the complexion changes’—if one wishes, a description of salt-induced hypertension.
Today this well founded view has gained widespread, but not universal, acceptance. In their book, MacGregor and de Wardener referred to salt as ‘Neptune's poisoned chalice’ [5].
The relationship of salt intake and blood pressure
What is the evidence now that salt increases blood pressure and causes cardiovascular accidents—even in individuals without renal or endocrine disease?
One of the most convincing pieces of evidence is the recent experimental work of Denton on chimpanzees which share 99% of our genome. For 3 years, 26 animals in socially stable groups had been kept on a fruit and vegetable diet with low salt content. Subsequently they were switched for 27 months to increasing amounts of salt comparable with human intake. A highly significant, but individually variable, rise in blood pressure was observed. It was fully reversible after 6 months [6].
Is there evidence in humans? In one study, blood pressure was monitored in two Portuguese villages—one of which was exposed to a campaign advocating salt restriction, while the other was not [7]. Blood pressure increased over the years in the village with unchanged salt intake and decreased in the village with salt restriction—but this study can be criticized on several accounts.
A study on newborn babies, equally not beyond critique, is nevertheless impressive. When the babies were given salt-restricted baby food for 6 months compared with control food, a 2 mmHg blood pressure difference was seen at 25 weeks. When they had grown to adolescent age, the difference had risen to slightly more than 3 mmHg [8].
In the view of most investigators, the definite study on this issue is the DASH study (standing for: dietary approaches to stop hypertension). If salt intake was lowered from the usual 150 to a low 50 mmol per day, in the overall cohort systolic blood pressure decreased by 6.7 mmHg. The decrease was even more pronounced (–11 mmHg) in hypertensive individuals [9].
Cynics say that meta-analysis is to analysis what metaphysics is to physics. For what it is worth, a recent meta-analysis showed that reduction of salt intake by 3 g/day lowers systolic blood pressure by 5.6 mmHg in hypertensive and 3.5 mmHg in normotensive individuals [10]. The authors extrapolated that lowering salt intake by 3 g/day in the general population would reduce stroke by 13% and ischaemic heart disease by 10%. This calculation was based on the epidemiological analysis of the relationship between blood pressure and cardiovascular events by MacMahon.
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How does salt increase blood pressure? |
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The classical view was that when salt is ingested, increased thirst and water intake cause expansion of the plasma and extracellular volumes, raising cardiac output and tending to increase blood pressure. In the long run, through poorly understood mechanisms of autoregulation, peripheral resistance would increase, thus increasing blood pressure further. This delayed rise in blood pressure may underlie the phenomenon of the ‘lag phase’ originally proposed by Scribner to explain the delay in the blood pressure response to a positive sodium balance in dialysed patients [11].
This classical view is true, but because of confounding factors it is not the full truth. First Titze provided evidence that under ceratin circumstances, salt is stored to some extent in the body, especially in the skin, in an osmotically inactive form [12]. Secondly, we know today that the compensatory increase of the production of the vasodilatory nitric oxide (NO) in response to salt intake is not uniform across rodent strains (and presumably also humans). In most strains, salt loading increases, and conversely salt restriction decreases, the activity of NOS3 (the endothelial isotype of nitric oxide synthase) as shown by Sato [13]. Humans who do not adequately react to salt-induced blood pressure increase by a compensatory increase of the production of vasodilatory and hypotensive NO are presumably the ones who are salt sensitive, i.e. develop hypertension on a high salt intake.
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Salt and oxidative stress |
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Hypertension in pre-disposed individuals is not the only downside of high salt intake. Sowers [14] recently summarized the evidence that on high salt the activity of NADPH oxidase and generation of reactive oxygen species (ROS) are increased. Paradoxically, a similar increase in oxidative stress is brought about by angiotensin II in response to low salt intake. ROS scavenge NO synthesized by endothelial cells. As a result, not only is vasodilatation insufficient, but the highly toxic peroxynitrite is also vasculotoxic.
However, matters are even more complex. The concentration of toxic oxygen species is the result of a balance between their synthesis and breakdown. Unfortunately, high salt stimulates the synthesis via NAD(P)oxidase and at the same time inhibits the breakdown by superoxide dismutase, as recently documented by Kitikayara in the kidney [15]. In his study, altered expression of these enzymes was accompanied by increased oxidative stress as reflected by increased urinary excretion of 8-isoprostane, a state of the art lipid marker of oxidative stress.
However, apart from the creation of oxidative stress, there are numerous other mechanisms through which high salt intake can mediate tissue damage: higher expression of AT1 receptors, higher local synthesis of aldosterone in the heart and the vessels, increased protein kinase C and ERK activity, etc. [16,17].
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Salt and cardiovascular target organ damage |
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Are the adverse effects of high salt on potential pathomechanisms translated into an increased frequency of target organ damage and cardiovascular as well as renal events?
Kupari showed years ago that in young men, sodium intake lower or higher than 148 mmol/day was a determinant of left ventricular mass [18]. This effect was amplified in the presence of high systolic blood pressure. This finding has been confirmed more recently by others [19,20]. Individuals on high sodium intake had a higher left ventricular mass index, higher albumin excretion and higher pulse pressure; furthermore, a steeper slope was found for the relationship between systolic blood pressure and these indices. In other words, high salt provoked an overshooting reaction of target organ damage to blood pressure [21].
Is there evidence for an impact on hard end-points?
In a Finnish study, sodium intake increased the risk of coronary heart disease and all-cause mortality independently of blood pressure: a sodium intake higher by 100 mmol/day increased the risk of coronary heart disease by 50% and all-cause mortality by 20% [22].
This observation has been confirmed in a recent meta-analysis: high sodium intake caused higher all-cause mortality, stroke incidence and coronary mortality, but only in the obese. So obesity is apparently an ancillary condition: in the overweight individual, but not in the individual who is not overweight, the stroke rate was double, coronary heart disease higher by 50% and all-cause mortality higher by 32% [23].
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Salt and progression of renal damage |
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Although in the distant past reduction of dietary salt intake was a cornerstone of the treatment of patients with renal disease [24], there is a deplorable lack of controlled data in the more recent nephrological literature on this topic [25–27].
One recent piece of evidence comes from the PREVEND study. In the general population of Groningen, The Netherlands, progressively higher rates of urinary albumin excretion were associated with progressively higher rates of sodium excretion [28], particularly if the body mass index was elevated—a hint that obesity plays a role. Reducing salt intake reduced albuminuria in hypertensive blacks, but the concomitant blood pressure decrease renders interpretation difficult [29]. A correlation between sodium excretion and albuminuria has also been observed in diabetic patients [30].
There is more information available from experimental studies. In the model of the uninephrectomized spontaneously hypertensive (SHR) rat, Benstein [31] noted that high glomerular capillary pressures and kidney hypertrophy were prevented by low salt diet and this could not be imitated with hydrochlorothiazide administration. Furthermore, in subtotally nephrectomized Munich Wistar rats, a low salt diet caused less of an increase in glomerular volume and signs of glomerular damage [32]. The beneficial effect of reducing dietary salt intake on progression has also been documented more recently in the model of antithymocyte serum glomerulonephritis [33].
A series of experimental studies provided insight into the underlying molecular mechanisms and documented that the balance of the glomerular signalling via transforming growth factor-ß (TGF-ß) and NOS3 was modulated by dietary salt intake promoting endothelial cell damage and progressive glomerular injury [34,35].
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The hunger for salt |
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To provide a balanced view, one must also have a look at the opposite of modern salt excess, i.e. salt deficiency. The physiologist Manley noted in the 19th century that salt hunger, the yearning for salt, was common at least in herbivorous animals. He wrote: ‘The universal existence of an appetite for salt surely indicates that the substance serves more important functions than that of merely gratifying the palate’ [36].
It may be of interest that many mineral springs were discovered when hunters observed that herbivorous animals frequented salt-containing springs, such as a stag (in Teinacher Hirschquelle), a pig (Salzsau discovering the salina of Lüneburg) and chamois (observed by a hunter to lick rock which led to the discovery of the salt rock near Hall in Tirol). Even the domestication of animals was explained by Denton [36] by the fact that wild animals are attracted by the salt content of human urine.
There is also contemporaneous evidence for this. Canadian woodcutters found that porcupines gnawed the veranda posts of their huts when they had misused them as pissoirs, and alpinists know that sweat-soaked pullovers spread on a rock will attract goats and chamois. Even the grooming of monkeys which is often attributed to hunting for fleas is a reflection of the search for salty skin secretions, and this has been proven by the fact that grooming intensifies when salt is put on the fur.
Does salt hunger also exist in humans?
After the first expedition to Senegal, Valentin Fernandez wrote: ‘The chiefs trade more gold for salt than for anything else (actually one kg gold for one kg salt). They need the salt for their cattle and for themselves. They state that without salt neither they nor their cattle will survive and prosper.’
The question then arises: if nature made salt-hungry animals and individuals search so desperately for salt, could low salt intake also be deleterious?
Alderman reported that individuals in the lowest tertile of urinary sodium excretion had the highest rate of myocardial infarction, both at age less and more than 55 years [37]. He put forward the hypothesis that low salt aggravated the coronary risk by increasing angiotensin II.
Experimental evidence for the hypothesis that extremely low salt intake has negative consequences is provided by a recent study of Ivanovski [38]. In the genetically atherosclerosis-prone apo E-deficient mouse, they noted that dietary salt restriction accelerated atherosclerosis. On regular salt intake, the total area of aortic lesions was significantly less than on low salt.
Another example of adverse effects of low salt is the study of Battista [39]: if pregnant rats were exposed to extreme dietary sodium restriction, the offspring were born with fewer glomeruli and nephrons. In adult age, they developed hypertension.
That the finding of fewer nephrons is not only relevant in the rat is suggested by our observation of oligomeganephrony in patients with essential hypertension who had fewer, but bigger glomeruli [40]. Indirect evidence also suggests that maternal malnutrition increases the renal risk of the offspring [41], although a specific role for low salt intake has not been proven.
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Appropriate salt intake—a matter of balance |
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Oxidative stress at both extremes of sodium balance calls for the selection of an optimum salt intake as a compromise between two adverse effects. As suggested by Sowers [14], a balance must be struck between too little and too much salt intake. One has to select an intake where the stimulation of the renin–angiotensin system on the one hand and the generation of oxidative stress on the other hand are minimal. It was presumably this consideration which led the European Society of Hypertension and European Society of Cardiology as well as other societies to postulate modest reduction of salt (6 g/day of sodium chloride) with a concomitant increase in potassium intake [42].
In my opinion, the issue of optimal salt intake is not an object for acrimonious controversies, but a challenge for rational reasoning and balanced decision making.
Conflict of interest statement. None declared.
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Accepted in revised form: 13.10.05
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