Dietary
salt (sodium)
Louis
Tobian,
Jr.,
Kinds
of evidence
Epidemiological
M.D.,
topic
and hypertension
leader
evidence
The highest incidence of hypertension is found in northern Japan where the sodium intake is above 400 mEq (100 mEq sodium = 5.8 g sodium chloride). However, some 20 primitive societies ingesting low-sodium intakes (10 to 60 mEq/day) have virtually no hypertension. In addition, susceptible individuals in primitive populations that change from low- to high-sodium intakes as acculturation occurs also develop hypertension. The fact that other primitive people with sodium intakes similar to those in industrialized populations such as the United States (100 to 200+ mEq/day) have a prevalence of hypertension similar to that in the United States suggests that salt itself, rather than differences in life style and other eating habits, is responsible for the prevalence of hypertension in “high-sodium” societies. In high-sodium societies the increase in blood pressure with childhood growth is more abrupt than the rate of rise in “low-sodium” populations. By the age of 18, roughly 10% of school children in industrialized societies have a systolic pressure above 140 or a diastolic pressure above 90. Thereafter, blood pressure rises progressively from 20 to 70 years of age in high-sodium societies, while in low-sodium societies blood pressures tend to stay at the same level over this age span. Hypen..nsion tends to cluster in families. In a high-sodium culture with sodium intakes of 125 to 250 mEq/day, it is clear that there are individual salt sensitivities, since those who do and others who do not develop hypertension have roughly similar sodium intakes. For reasons not understood, blacks have a higher prevalence of hypertension than whites, even though the two races consume the same high-sodium diet. Potassium intakes are generally low in high-sodium popThe American
Journal
of Clinical
Nutrition
32: DECEMBER
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
ulations and high in low-sodium populations; other cations may also be of importance. The ratio of sodium to potassium in the diet and its relationship to high blood pressure requires further investigation. In the majority of normotensive individuals, an intake of as much as 300 mEq/day of sodium will not induce hypertension. In contrast, the minority that does develop hypertension appears to have a genetically determined susceptibility to salt loading and manifest the disease on intakes of 125 to 250 mEq/day. However, as shown in primitive populations, a life-long diet with less than 50 mEq/day of sodium fails to reveal those individuals who have salt sensitivity, and thus hypertension fails to appear. Once salt-induced hypertension has been present for a number of years, restricting sodium to 60 mEq daily may only partially lower the level of blood pressure. Thus, it appears that a lower level of dietary sodium intake is required to correct established hypertension than to prevent its appearance in the first place. Animal
experimentation
Although spontaneous hypertension has not often been observed in free-living animals, experimental hypertension has been readily produced in a variety of experimental animals by the feeding of sodium chloride, i.e., the monkey, chicken, and rat. It is in the rat that most experimental observations have been made. These include the following important results. 1) The tendency to develop sodium-induced hypertension is genetically determined. Susceptible rats develop hypertension on a high-sodium intake, but remain normotensive on a low-sodium diet, while resistant strains of rats do not become hypertensive on a high-sodium diet. By selective breeding, strains of salt-sensitive and salt-resistant rats
1979,
pp. 2659-2662.
Printed
in U.S.A.
2659
SODIUM
2660
reduction of renal mass, as in the rat, especially in dialyzed and nephrectomized patients). Thus, metabolic studies and clinical trials have established a central role of dietary sodium in the correction or amelioration of mild to severe hypertension. The action of antihypertensive drugs is potentiated by a low-sodium diet. Diuretic agents slightly deplete the body of sodium in hypertensive individuals and subsequently the blood pressure falls. This antihypertensive effect is very likely related to sodium intake, since sodium in excess of 350 mEq/ day can completely prevent the diuretic-related lowering of blood pressure. The mechanism by which the blood pressure is lowered is probably the same as that which operates on a low-sodium diet.
have been made available for experimental studies of mechanisms. 2) In rats susceptible to sodium-induced hypertension, the blood pressure elevation is directly related to dose (salt intake). 3) Increasing the potassium in the diet modifies but may not eliminate the blood pressure elevating effects of a given amount of dietary sodium. 4) A diminution of renal mass accelerates the hypertensive effect of a given amount of dietary sodium. Similarly, the addition of exogenous salt-retaining steroid hormones potentiates the hypertensive effect of sodium in the diet. Conversely, a very low intake of sodium completely prevents the hypertension that can otherwise be brought out by large doses of salt-retaining adrenal steroids. 5) The end-organ damage from sodiuminduced hypertension is similar to that found in human pathology: arteriolosclerosis, gbmerular sclerosis, renal failure, and cardiac hypertrophy. 6) Hypertensive animals only develop arterial lesions similar to those of human atherosclerosis when they are fed an atherogenic diet and develop hyperlipidemia. Under such circumstances, hypertension accelerates the atherosclerotic process.
with and
Human
Consistency population
experimentation
As in the rat, only certain human beings become hypertensive on high intakes of dietary sodium. Thus, the feeding of sodium intakes of 200 to 400 mEq/day to white normotensive volunteers for 4 weeks does not always raise the blood pressure. However, borderline hypertensives develop increased blood pressure when fed these loads of dietary sodium; when this extra sodium is removed from the diet, the blood pressure falls. The feeding of very large amounts of dietary sodium (800 mEq/day and upwards) to normotensive volunteers uniformly increases the blood pressure. It is well established that the reduction of dietary sodium in hypertensive individuals produces a lowering of blood pressure. Indeed, the first demonstration that malignant hypertension could be successfully treated involved the use of a drastically low-sodium diet (10 mEq/day). Patients with renal insufficiency are particularly sensitive to the hypertensive effects of dietary sodium (such as
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
Quality
and strength
Consistency
among
of the evidence various
population
groups
Throughout the world the relationship between dietary sodium and prevalence of hypertension is consistent, with the highest disease rates in populations ingesting the most sodium. There are no known exceptions to the association of very low sodium intakes and virtual absence of essential hypertension. among
individuals
within
a given
The tendency to develop hypertension is a function of individual susceptibility and salt intake. Thus, the intake of sodium in Western urbanized areas (150 to 250 mEq/day) is sufficient to permit the full expression of hypertension in genetically susceptible individuals. It is not known with certainty what fraction of the American population is “salt sensitive.” An estimated 17% of adult Americans become hypertensive on typical American intake of sodium of 150 to 250 mEq/ day; presumably this 17% is the salt-sensitive subset of the American population. At present there is no simple way to predict which individuals will react to the average American sodium intake by becoming hypertensive and thus might be benefited by a lower intake. Autopsy
data
in man
There are no autopsy data that bear on the relationships of reduced or increased salt intakes to amelioration or exacerbation of tissue
SODIUM damage, although the pathological changes observed in those who were clinically hypertensive are characteristic. The measurement of blood pressure rather than postmortem data has been the main index of the relationship between sodium intake and hypertensive disease. Strength
Biological
of the association
Between and within population groups there is a strong association between sodium intake and the prevalence of hypertension. However, the size of the salt-sensitive population is not known with precision, nor can individual sensitivities to salt intake be easily identified for the sake of carrying out large controlled trials of a low sodium intake. Independence
of the association
It is well demonstrated various human populations,
renal disease influences
and in patients with intake independently sure. Temporal
The
carried dicated tension dietary
in
that sodium blood pres-
strength
Sodium ingestion ment of hypertension sitive to salt intake. Effect
in animals and in hypertensives
precedes in those
the who
developare sen-
of new exposure few prospective studies that have been out in migrant populations have inthat an increased incidence of hyperfollows an increased consumption of sodium.
Preventive
effect
of removal
No primary controlled trial of sodium reduction has been attempted in human populations. Improvement
effect
of removal
The reduction of dietary sodium in hypertensive patients usually results in lowered blood pressure, improves the control of the blood pressure by diuretics, and reduces the incidence and severity of the sequelae of hypertension. Animal
models
Dietary sodium induces hypertension animals. Salt-sensitivity and salt-resistance are genetically controlled.
in
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
2661
explanation
The mechanism of experimental salt-induced hypertension may relate to some impairment of the excretion of sodium by the kidneys of susceptible rats. When such an animal is exposed to high levels of dietary sodium, an initial sodium retention induces a rise in blood pressure that is followed by natriuresis and normalization of blood pressure. A nonrenal, nonadrenal, sodium-retaining hormone may be involved in this tendency to sodium retention. Furthermore, the content of sodium in the arterial wall is usually increased. This electrolyte change may sensitize the artery to vasopressor stimuli. Other changes include an increase in plasma and extracellular fluid volume. An excessive release of norepinephrime at sympathetic nerve endings and the appearance of a circulating humoral vasoconstrictor occur in rats with salt-induced hypertension; these changes may in turn contribute to the peripheral arteriolar vasoconstriction in salt-induced hypertension. In man the mechanism of the hypertensive effect of dietary sodium begins with an initial transitory retention of sodium in body tissues and fluids that is followed by an increase in blood volume and extracellular fluid volume. The increase in “effective” body sodium usually causes a rise in blood pressure that in one study was also characterized by an increase in peripheral vascular resistance. In a few cases, hypertension is accentuated by an increase in cardiac output. It has recently been shown in normotensive volunteers that a progressive increase in mean blood pressure and cardiac output accompanies stepwise rises in dietary sodium intake from 10 to 1600 mEq/ day. Risks and benefits sodium
of reducing
the
intake
of
The sodium ion is an essential nutrient, but the amounts commonly consumed in the Western world exceed the minimum required by 10- to 40-fold. Reduction of the intake of dietary sodium to 60 mEq/day may lower the blood pressure of a hypertensive individual whose previous sodium intake was high, and offers the likelihood of benefit for the roughly one-sixth of the population who can be expected to develop essential hypertension.
2662
SODIUM
However, the advantages of preventing hypertension by reduction of salt intake in the entire population as compared with early detection and treatment of new cases have not been clarified. The risk of a low-sodium diet to the rare individual with salt-losing renal disease or adrenal insufficiency can be profound, but it is anticipated that these sick individuals would be recognized as having unusual dietary sodium requirements and would be spe-
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
cially treated. Occasionally, intense sweating secondary to physical exertion, or salt loss with diarrhea or vomiting, may lead to severe depletions in persons maintained on intakes as low as 60 mEq/day. Since a 60 mEq sodium diet has not been applied prospectively in wide segments of the American population, it is possible that certain subsets of the population who may need higher levels of dietary sodium, such as the elderly and the pregnant, may be identified.
a
salt (sodium)
Louis
Tobian,
Jr.,
Kinds
of evidence
Epidemiological
M.D.,
topic
and hypertension
leader
evidence
The highest incidence of hypertension is found in northern Japan where the sodium intake is above 400 mEq (100 mEq sodium = 5.8 g sodium chloride). However, some 20 primitive societies ingesting low-sodium intakes (10 to 60 mEq/day) have virtually no hypertension. In addition, susceptible individuals in primitive populations that change from low- to high-sodium intakes as acculturation occurs also develop hypertension. The fact that other primitive people with sodium intakes similar to those in industrialized populations such as the United States (100 to 200+ mEq/day) have a prevalence of hypertension similar to that in the United States suggests that salt itself, rather than differences in life style and other eating habits, is responsible for the prevalence of hypertension in “high-sodium” societies. In high-sodium societies the increase in blood pressure with childhood growth is more abrupt than the rate of rise in “low-sodium” populations. By the age of 18, roughly 10% of school children in industrialized societies have a systolic pressure above 140 or a diastolic pressure above 90. Thereafter, blood pressure rises progressively from 20 to 70 years of age in high-sodium societies, while in low-sodium societies blood pressures tend to stay at the same level over this age span. Hypen..nsion tends to cluster in families. In a high-sodium culture with sodium intakes of 125 to 250 mEq/day, it is clear that there are individual salt sensitivities, since those who do and others who do not develop hypertension have roughly similar sodium intakes. For reasons not understood, blacks have a higher prevalence of hypertension than whites, even though the two races consume the same high-sodium diet. Potassium intakes are generally low in high-sodium popThe American
Journal
of Clinical
Nutrition
32: DECEMBER
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
ulations and high in low-sodium populations; other cations may also be of importance. The ratio of sodium to potassium in the diet and its relationship to high blood pressure requires further investigation. In the majority of normotensive individuals, an intake of as much as 300 mEq/day of sodium will not induce hypertension. In contrast, the minority that does develop hypertension appears to have a genetically determined susceptibility to salt loading and manifest the disease on intakes of 125 to 250 mEq/day. However, as shown in primitive populations, a life-long diet with less than 50 mEq/day of sodium fails to reveal those individuals who have salt sensitivity, and thus hypertension fails to appear. Once salt-induced hypertension has been present for a number of years, restricting sodium to 60 mEq daily may only partially lower the level of blood pressure. Thus, it appears that a lower level of dietary sodium intake is required to correct established hypertension than to prevent its appearance in the first place. Animal
experimentation
Although spontaneous hypertension has not often been observed in free-living animals, experimental hypertension has been readily produced in a variety of experimental animals by the feeding of sodium chloride, i.e., the monkey, chicken, and rat. It is in the rat that most experimental observations have been made. These include the following important results. 1) The tendency to develop sodium-induced hypertension is genetically determined. Susceptible rats develop hypertension on a high-sodium intake, but remain normotensive on a low-sodium diet, while resistant strains of rats do not become hypertensive on a high-sodium diet. By selective breeding, strains of salt-sensitive and salt-resistant rats
1979,
pp. 2659-2662.
Printed
in U.S.A.
2659
SODIUM
2660
reduction of renal mass, as in the rat, especially in dialyzed and nephrectomized patients). Thus, metabolic studies and clinical trials have established a central role of dietary sodium in the correction or amelioration of mild to severe hypertension. The action of antihypertensive drugs is potentiated by a low-sodium diet. Diuretic agents slightly deplete the body of sodium in hypertensive individuals and subsequently the blood pressure falls. This antihypertensive effect is very likely related to sodium intake, since sodium in excess of 350 mEq/ day can completely prevent the diuretic-related lowering of blood pressure. The mechanism by which the blood pressure is lowered is probably the same as that which operates on a low-sodium diet.
have been made available for experimental studies of mechanisms. 2) In rats susceptible to sodium-induced hypertension, the blood pressure elevation is directly related to dose (salt intake). 3) Increasing the potassium in the diet modifies but may not eliminate the blood pressure elevating effects of a given amount of dietary sodium. 4) A diminution of renal mass accelerates the hypertensive effect of a given amount of dietary sodium. Similarly, the addition of exogenous salt-retaining steroid hormones potentiates the hypertensive effect of sodium in the diet. Conversely, a very low intake of sodium completely prevents the hypertension that can otherwise be brought out by large doses of salt-retaining adrenal steroids. 5) The end-organ damage from sodiuminduced hypertension is similar to that found in human pathology: arteriolosclerosis, gbmerular sclerosis, renal failure, and cardiac hypertrophy. 6) Hypertensive animals only develop arterial lesions similar to those of human atherosclerosis when they are fed an atherogenic diet and develop hyperlipidemia. Under such circumstances, hypertension accelerates the atherosclerotic process.
with and
Human
Consistency population
experimentation
As in the rat, only certain human beings become hypertensive on high intakes of dietary sodium. Thus, the feeding of sodium intakes of 200 to 400 mEq/day to white normotensive volunteers for 4 weeks does not always raise the blood pressure. However, borderline hypertensives develop increased blood pressure when fed these loads of dietary sodium; when this extra sodium is removed from the diet, the blood pressure falls. The feeding of very large amounts of dietary sodium (800 mEq/day and upwards) to normotensive volunteers uniformly increases the blood pressure. It is well established that the reduction of dietary sodium in hypertensive individuals produces a lowering of blood pressure. Indeed, the first demonstration that malignant hypertension could be successfully treated involved the use of a drastically low-sodium diet (10 mEq/day). Patients with renal insufficiency are particularly sensitive to the hypertensive effects of dietary sodium (such as
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
Quality
and strength
Consistency
among
of the evidence various
population
groups
Throughout the world the relationship between dietary sodium and prevalence of hypertension is consistent, with the highest disease rates in populations ingesting the most sodium. There are no known exceptions to the association of very low sodium intakes and virtual absence of essential hypertension. among
individuals
within
a given
The tendency to develop hypertension is a function of individual susceptibility and salt intake. Thus, the intake of sodium in Western urbanized areas (150 to 250 mEq/day) is sufficient to permit the full expression of hypertension in genetically susceptible individuals. It is not known with certainty what fraction of the American population is “salt sensitive.” An estimated 17% of adult Americans become hypertensive on typical American intake of sodium of 150 to 250 mEq/ day; presumably this 17% is the salt-sensitive subset of the American population. At present there is no simple way to predict which individuals will react to the average American sodium intake by becoming hypertensive and thus might be benefited by a lower intake. Autopsy
data
in man
There are no autopsy data that bear on the relationships of reduced or increased salt intakes to amelioration or exacerbation of tissue
SODIUM damage, although the pathological changes observed in those who were clinically hypertensive are characteristic. The measurement of blood pressure rather than postmortem data has been the main index of the relationship between sodium intake and hypertensive disease. Strength
Biological
of the association
Between and within population groups there is a strong association between sodium intake and the prevalence of hypertension. However, the size of the salt-sensitive population is not known with precision, nor can individual sensitivities to salt intake be easily identified for the sake of carrying out large controlled trials of a low sodium intake. Independence
of the association
It is well demonstrated various human populations,
renal disease influences
and in patients with intake independently sure. Temporal
The
carried dicated tension dietary
in
that sodium blood pres-
strength
Sodium ingestion ment of hypertension sitive to salt intake. Effect
in animals and in hypertensives
precedes in those
the who
developare sen-
of new exposure few prospective studies that have been out in migrant populations have inthat an increased incidence of hyperfollows an increased consumption of sodium.
Preventive
effect
of removal
No primary controlled trial of sodium reduction has been attempted in human populations. Improvement
effect
of removal
The reduction of dietary sodium in hypertensive patients usually results in lowered blood pressure, improves the control of the blood pressure by diuretics, and reduces the incidence and severity of the sequelae of hypertension. Animal
models
Dietary sodium induces hypertension animals. Salt-sensitivity and salt-resistance are genetically controlled.
in
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
2661
explanation
The mechanism of experimental salt-induced hypertension may relate to some impairment of the excretion of sodium by the kidneys of susceptible rats. When such an animal is exposed to high levels of dietary sodium, an initial sodium retention induces a rise in blood pressure that is followed by natriuresis and normalization of blood pressure. A nonrenal, nonadrenal, sodium-retaining hormone may be involved in this tendency to sodium retention. Furthermore, the content of sodium in the arterial wall is usually increased. This electrolyte change may sensitize the artery to vasopressor stimuli. Other changes include an increase in plasma and extracellular fluid volume. An excessive release of norepinephrime at sympathetic nerve endings and the appearance of a circulating humoral vasoconstrictor occur in rats with salt-induced hypertension; these changes may in turn contribute to the peripheral arteriolar vasoconstriction in salt-induced hypertension. In man the mechanism of the hypertensive effect of dietary sodium begins with an initial transitory retention of sodium in body tissues and fluids that is followed by an increase in blood volume and extracellular fluid volume. The increase in “effective” body sodium usually causes a rise in blood pressure that in one study was also characterized by an increase in peripheral vascular resistance. In a few cases, hypertension is accentuated by an increase in cardiac output. It has recently been shown in normotensive volunteers that a progressive increase in mean blood pressure and cardiac output accompanies stepwise rises in dietary sodium intake from 10 to 1600 mEq/ day. Risks and benefits sodium
of reducing
the
intake
of
The sodium ion is an essential nutrient, but the amounts commonly consumed in the Western world exceed the minimum required by 10- to 40-fold. Reduction of the intake of dietary sodium to 60 mEq/day may lower the blood pressure of a hypertensive individual whose previous sodium intake was high, and offers the likelihood of benefit for the roughly one-sixth of the population who can be expected to develop essential hypertension.
2662
SODIUM
However, the advantages of preventing hypertension by reduction of salt intake in the entire population as compared with early detection and treatment of new cases have not been clarified. The risk of a low-sodium diet to the rare individual with salt-losing renal disease or adrenal insufficiency can be profound, but it is anticipated that these sick individuals would be recognized as having unusual dietary sodium requirements and would be spe-
Downloaded from https://academic.oup.com/ajcn/article-abstract/32/12/2659/4692412 by Queen Mary University of London user on 20 March 2018
cially treated. Occasionally, intense sweating secondary to physical exertion, or salt loss with diarrhea or vomiting, may lead to severe depletions in persons maintained on intakes as low as 60 mEq/day. Since a 60 mEq sodium diet has not been applied prospectively in wide segments of the American population, it is possible that certain subsets of the population who may need higher levels of dietary sodium, such as the elderly and the pregnant, may be identified.
a
