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BLOG: May 2010
Is sodium bad for you?
Sodium is bio-electrolyte essential not only for maintaining optimum health, but for the very survival. No one disputes that fact. Without it, the subtle flow of electrical currents supporting life - called bio-electricity - would be irreparably interrupted.
As we all know, nearly all of our sodium intake comes from salt, or, chemically, sodium chloride. Chloride itself is an essential mineral, so it is not in question whether we need salt, or not - only what is the safe limit to its intake. This is very important question to answer for every essential nutrient, because we need to consume them every day - or nearly so - for life. And, as we know very well,
excess of any nutrient is invariably unhealthy.
When is it that sodium intake reaches that level?
The current official guidelines (DRI) draws the line at 2.3g per day. That is equivalent of 5.75g of salt, with the recommended intake for adults and adolescents being 1.5g/day of sodium, or 3.75g of salt.
How did they come up with this figure?
Its origin is the estimated sodium intake of our primitive ancestors, and the remaining hunter-gatherer societies. The official figures closely coincide with the data collected by Dahl, mostly during the 1950s, indicating that the highest daily intake of these primitive groups (with practically no salt added to their food) was about 5g of salt, with some consuming less than 1g (2g and less than 0.4g of sodium, respectively, Possible role of salt intake in the development of essential hypertension, 1960).
That is roughly several times less than modern-day salt consumption - typically 8-12g/day, and up to 30g/day in some world regions - and excessive in comparison.
Based on that, significantly higher sodium consumption in civilized societies was quickly characterized as overconsumption, and associated with hypertension. The hasty hypothesis had no sufficient factual grounds at the time, but that hole was "filled" with subsequent experiments, mainly on rodents, sparing no lengths in producing desired result.
Additional support came from small-scale trials on hypertensive patients with renal insufficiency, apparent success of low-salt diets (which also happened to be low in calories and fat, and high in potassium and nutrients in general), and scanty data of the relation between salt intake and hypertension rate for several selected populations.
Although either not relevant to the sodium consumption of human populations, unreliable, or insufficient for any definitive conclusions, these data were taken as the
proof of sodium's evil effects at its present consumption level,
forming the official view on the subject of salt intake in the Western countries.
This is how the whole salt-hypertension controversy had started. Since that time, the bulk of research indicates that there is no basis to consider typical salt intakes in developed countries generally excessive.
That higher sodium intake tends to raise blood pressure seems to be well documented, but the effect is generally negligible. This doesn't mean that it is negligible for everyone. How the body actually reacts to the changes in salt intake varies individually.
Back in the 1980s, when much of the focus was still on the salt-hypertension link, a standard defining blood pressure salt sensitivity (BPSS) based on body's reaction on higher salt intake was set as follows (Weinberger et al. 1986):
√ salt-sensitive: blood pressure is more than 10mm Hg higher in salt-loaded vs. salt-depleted state (defined as administration of 2 liters of saline - normally containing 18g of salt - and low-salt diet of 0.575 g/day, respectively)
√ normal: between 5 and 10 mm Hg increase
√ salt-resistant: less than 5 mm Hg increase
The study found that 51% of hypertensive and 26% of normotensive participants in the total of 203 were salt sensitive, while 33% and 58%, respectively, were salt-resistant. According to these numbers, about one in every two hypertensive persons is salt-sensitive, and 1 in 4 among normotensive individuals (1 in 3 for African-American sub-population). That would put a total of salt-sensitive individuals in the U.S. at nearly 100 million. One in three.
This is the accepted mainstream view on the subject of salt-sensitivity.
Later studies indicated that BPSS is a significant risk factor for both, hypertensive and normotensive individuals (Weinberger et al. 2001). Among the former, incidence of cardiovascular events is three times higher for those with BPSS; among the latter, those with BPSS develop hypertension more frequently.
On top of that, the same study found that BPSS increases mortality in normotensive individuals as well. That implicates multiple mechanisms through which higher sodium (salt) intake may negatively affect health.
But the results of some other studies not only shed somewhat different light on BPSS, but also question both completeness and objectivity of this mainstream view. Specifically, a 1993 study with 163 normotensive participants (mean age 38y), observed that within the salt resistant category there is significant hidden sub-category: some people - and not a few of them - actually
have their blood pressure decrease with higher salt intake.
Noting that all participants here were normotensive, the majority, 66%, were salt-resistant, 18% were salt-sensitive, and 15% were "counter-regulators": they had significant drop in blood pressure with higher salt intake (Overlack et al, 1993).
This study had somewhat different procedures and criteria than the 1986 Weinberger study:
∙ participants were white, non-obese and normotensive, in order to avoid confounding; Weinberger et al. had unknown proportion of obese, and relatively large proportion (25%) of black participants, nearly all females
∙ low-salt regime had 20 mmol (0.46g) of sodium (i.e. 1.15g of salt), double that in Weinberger et al. (high-salt regime was nearly identical, 17.25g vs. 18g of salt in Weinberger et al.)
∙ participants were on high- and low-salt regime for a week each, as opposed to a single day in Weinberger et al.
∙ salt-sensitive was defined as blood pressure increase over 5mm Hg on high-salt regime, salt-resistant with blood pressure change between 5mm Hg increase and 5mm HG decrease, and counter-regulator with more than 5mm Hg blood pressure decrease on high-salt diet
In all, despite lowering the bar for salt-sensitivity from 10 to 5 mm Hg blood pressure increase, Overlack et al. had significantly lower proportion of salt-sensitive participants (18 vs. 26%), compared to the normotensive group in Weinberger et al. Part of the discrepancy - but not all - can be explained by significantly larger proportion of women (which in both studies had higher rate of salt sensitivity than men), as well as the presence of black participants in the latter study.
Also, it is possible that the effect lessens with time, i.e. that is more pronounced in 24-period (Weinberger et al.) than in a week-long exposure (Overlack et al).
As a side note, worth mentioning is the contradictory observation in Weinberger et al. that the efficiency of haptoglobin phenotype tend to be inversely related to the incidence of salt sensitivity in normotensive, but commensurate to it in hypertensive individuals (heptaglobin is body protein that binds and removes from circulation free hemoglobin, which otherwise could injure the kidneys; haptoglobin function may have effect on cardiovascular and other diseases).
Overlack also had a subsequent smaller study, this time with 46 white, non-obese participants with essential hypertension. Again, it gave significantly different picture than Weinberger et al. 1986. Applying the same criteria for salt sensitivity, salt resistance and counter-regulation as in their first study, the respective percentages were 23.9, 58.7 and 17.4% - not substantially different than those with normotensive participants (Overlack et al. 1995).
Among salt-sensitive participants, 10 out of 11 were older than the median 45y age (for comparison, median age in Weinberger et al. 1986 was 42.6y and 27.4y for hypertensive and normotensive participants, respectively). Median arterial blood pressure for all participants increased at high vs. restricted salt intake by 1.8 mm Hg (from 101.9 to 103.7).
Here is comparison table with the main features and outcomes of Overlack et al. vs. Weinberger et al.
While these studies are too small, and of too short duration to provide reliable data for the general population (despite that, Weinberger et al. was promoted to a representative of the general population), their results clearly indicate that:
(1) the accepted picture of the overall extent of salt sensitivity in the general population may be exaggerated
(2) reaction to high-salt intake is heterogeneous for both, hypertensives and normotensives, with the majority in both groups being salt-resistant, while the proportion of those reacting either with increased or decreased blood pressure is smaller, but not negligible, and
(3) the average increase in mean arterial blood pressure between restricted (1.15g a day) and high (17.25g a day) salt intake is nearly insignificant, implying that even halving the present average salt consumption in the U.S. (9-10g a day)
is not likely to produce measurable effect
With these conclusions, let's focus at the possible mechanisms through which higher salt intake and related regulatory responses of the body may be affecting blood pressure.
For reasons explained earlier, most of attention in this respect was concentrated on a relatively small part of the picture, i.e. the increase in blood pressure following exposures to high salt intake level. As a result, more is known about possible mechanisms for this effect .
While nothing is known for certain, the common trigger is thought to be inefficiency of the kidneys to excrete excess sodium (in animal experiments, hypertension travels with the donor kidney). Resulting sodium retention raises its plasma level which through multiple possible mechanisms can raise blood pressure.
This poses two distinct questions: (1) what causes kidney inefficiency, and (2) how the elevated plasma sodium triggers hypertension?
Causes of sodium retention
These are some of the most likely causes of the reduced efficiency of the kidneys to excrete sodium identified so far:
▶ reduced number of nephrons (coiled tubules - about 1 million of them - inside kidneys that filter waste materials from the blood, producing urine), either as a prenatal condition, or caused by post-natal developments
▶ elevated sodium level within kidneys, either as a result of pathological bottleneck such as reduced number of nephrons, or simply due to heightened intake - or both - may activate pro-inflammatory cytokines and chemokines in proximal tubular cells, may cause oxidative stress by activating ROS-producing NADH oxidase enzymes, or blood vessel constriction by inhibiting kidney arginine transport and nitric oxide synthesis; elevated renal inflammation, oxidative stress and restricted blood flow all can impair the efficacy of sodium excretion, more so combined (if extensive, it can also result in post-natal reduction of nephron units)
▶ elevated blood uric acid level, due to inefficient purines metabolism, or high-protein diet, which can activate renin-angiotensin-aldosterone system (the latter being adrenal hormone stimulating increase in the rate of sodium reabsorption by the kidneys), in addition to contributing to hypertension by causing endothelial dysfunction and smooth muscle cell proliferation; rising uric acid level in the population may be among chief factors behind increasing incidence of hypertension - as many as 90% of the children with essential hypertension have high uric acid levels (Feig et al, 2006)
malfunctioning sodium channels and associated proteins in the
kidney due to genetic mutations and polymorphism; this includes:
▶ since insulin stimulates sodium reabsorption, elevated insulin level, due to insulin resistance (diabetes) or even high-glycemic diet, can also contribute to the development of salt sensitivity; study results are somewhat contradictory, but it may be at least in part due to a number of other factors possibly involved (elevated insulin also can alter calcium channels function by stimulating synthesis of endogenous aldehydes; this can result in higher level of cellular calcium, increasing contractility of heart and smooth muscle tissue around blood vessels)
Obviously, there are multiple possible causes of kidney inefficiency with respect to sodium excretion, and the subject is rather complex. Other factors can come into play, such as:
▪ stress-related sodium retention, which also can have multiple mechanism,
▪ endothelin B (ETB) function (body peptide stimulating dilation of blood vessel in the kidney as a response to elevated sodium level), possibly involving over-expression of endothelin A (ETA), a vaso-constrictor,
▪ inhibitory effect of metal ions, alone or combined, on sodium channels (research indicate that body's radical quenchers like glutathione, L-cysteine and EDTA can prevent or reverse such inhibition by "friendly" metals like zinc, copper, iron and cobalt, but not that caused by heavy"metals like lead and mercury), possible inhibition of sodium channel activity by dopamine, and others.
The second part of the puzzle is how, specifically, excess sodium trapped in the body as a result of renal insufficiency triggers hypertension.
From elevated sodium to elevated blood pressure
The oldest proposed mechanism is that sodium retention increases extracellular (fluid) volume, which in turn increases cardiac output; resulting blood overflow would cause vasoconstriction - and hypertension - as a result of body's autoregulatory action (Guyton et al, 1972). This hypothesis, however, hasn't been positively proven in subsequent studies.
Another possible effect related to the increased extracellular volume is subsequent raise in the level of endogenous substances (ouabain, marinobufagenin, and others) inhibiting membranal sodium (ion) channels, also called Na+/K+-ATPase pumps. The resulting increase in cellular sodium level can cause influx of calcium which, in turn, stimulates cardiac contractility and vasoconstriction. Since there is evidence of elevated endogenous sodium channel inhibitors in hypertensive individuals, this factor seems to be a part of the link between sodium retention and high blood pressure.
Similar inhibition of sodium channels can result from low magnesium levels.
Sodium could also directly affect blood pressure by causing hypertrophy of cardiac myoblast and vascular smooth muscle cells (Gu et al, 1998). This would also stimulate contractility of the heart and smooth muscles around blood vessels, elevating blood pressure.
Yet another sodium-hypertension link is found in the elevated sodium causing increase in TGF-β (Transforming Growth Factor) production, a body protein that, among other functions, controls (normally slows down) cellular proliferation. Among possible consequences are reduction in the number of nephron units and reduced blood vessel diameter. Either could make excretion of the excess sodium less efficient, and the latter, if systemic, could directly cause raise in blood pressure (assuming other factors unchanged). Research indicates that the effect of sodium on TGF-β production could be a viable mechanism contributing to hypertension.
Somewhat over-simplistic, but fairly popular mechanical "model" is that elevated blood pressure results from body's attempt to help the kidneys excrete the excess sodium by literally forcing it out through the capillaries. Such reaction is possible, and would require complex autoregulatory mechanism.
Summing it up, we can conclude that sodium retention leading into elevated blood pressure (retention itself does not necessarily produce this effect) may be most often related to compromised sodium metabolism, centered around kidneys, but that a number of other factors - some of them probably still not known - can significantly influence the outcome.
As for the mechanisms through which high salt intake causes the opposite reaction, i.e. drop in blood pressure, they have been little investigated. Their origins are likely to be as complex as of those causing blood pressure increase, hidden in the labyrinths of each individual metabolism.
It is known in clinical practice that some people have exactly the opposite reaction to salt loading than what the canonical water retention assumes:
it prompts their bodies to excrete fluids,
sometimes lots of it. In the process, sodium is lost too, and it may result in lowered blood pressure (in Overlack et al. the counter-regulators had 10% higher average sodium excretion than salt-resistant group, and 20% higher than salt-sensitive group).
Wide range of variations in individual metabolismt inevitably implies just as wide range of reactions to the same stimulus. It is very unlikely that the Overlack et al. results are either an error or gross deviation; certainly not more so than those of Weinberger et al. Hence we can reasonably assume that there is a sub-population in which higher salt intake would cause drop in blood pressure. Consequently, the possibility that salt intake reduction would cause blood pressure increase within this sub-population cannot be ruled out.
What is still quite uncertain is
whether salt-intake-related changes in blood pressure in studies subjects are permanent, or, at least in part, temporary.
Very few studies monitor the effect long enough to furnish meaningful indication in this respect. One of them is NLHBI-funded TOHP II (Trials of Hypertension Prevention), in which reduction of ~2.6g in daily sodium intake by study's overweight/obese participants was followed with 2.9/1.6 (systolic/diastolic) mm Hg blood pressure decrease after 6 months, diminishing to 1.3/0.9 mm Hg after 36 months.
In the NLHBI-sponsored Hypertension Prevention Trial (HPT, Shah et al. 1990), the change in mean systolic blood pressure went from -1.7 mm Hg after six months to +0.1 mm Hg after 18 months (follow-up analysis by Forster et al. points out difficulties in assessing accurate data, not only from self-reported intakes but from urine tests as well).
Gradual decrease of the effect could have been due to psychological factors (treatment "placebo" effect), body adaptation, difficulty of adhering to lower-salt diet, urine test inaccuracy (either due to natural day-to-day variations in salt intake, or deliberate decrease in salt consumption on the test day), or something else. The only certain thing is that we don't know whether the change in salt consumption has lasting effect on blood pressure - in those instances when it does have appreciable effect - or it vanishes longer-term.
So, what is the answer to the question: "Is sodium bad for you?". What we do know at this moment can be briefly summarized as follows:
∎ salt could affect blood pressure in a number of mechanisms
∎ for the majority of people, nearly two in three, the effect is insignificant in the wide range of sodium intake (0.4-7.2g/day, corresponding to 1-18g/day of salt), and
∎ the rest, that can be classified as "salt-sensitive", react to high salt intake either with relatively significant raise in blood pressure or - nearly as often - with significant blood pressure drop; it is not known whether or how these effects change long-term
This provides coarse information needed to grasp the big picture. Study results predominantly fit into this picture. Neither supports the notion that relatively small reduction in salt intake on the level of population would have appreciable positive impact either on hypertension rates or cardiovascular health.
But there is another source of information, outside the world of studies, that we can, and should turn to: the real world. Just how much is this data supporting - or not - salt hypothesis?
More in the following article.