Dietary Sodium Intake and Asthma: An Epidemiological and Clinical Review

T. D. Mickleborough; A. Fogarty

Disclosures

Int J Clin Pract. 2006;60(12):1616-1624. 

In This Article

Dietary Sodium and Asthma

It has been observed that asthma morbidity and mortality are greater in communities adopting a more Western lifestyle and in migrants as they move from rural underdeveloped to urban westernized areas.[27,28] Dietary intake of sodium chloride is typically high (averaging 7-10 g/day; 2.8-4 g/day of sodium)[29] in westernized areas and this excess salt intake is associated with other diseases of smooth muscle constriction such as hypertension.[30] The minimum recommended daily allowance for sodium in the USA is 500 mg/day,[31] with an upper limit of <2400 mg of sodium per day considered optimal[31] for health. In the UK, the recommended intake of sodium is <2.4 g/day,[32] a decision made mainly on the basis of the cardiovascular benefits to be derived by the population as a whole.

Stoesser and Cook[33] in 1938 were the first to propose a possible connection between salt consumption and the severity of chronic bronchial asthma. In a study, published in abstract form only, in which the numbers of subjects or other details were not provided, they observed that a low salt diet (LSD) contributed to a decrease in symptoms in children with severe asthma, and high salt diets resulted in an increase of symptoms. This study, while lacking in scientific rigour and pulmonary function data, did provide the first indication that dietary sodium chloride might play a role in modifying the severity of asthma.

Epidemiological Studies

Recognizing the possibility that a high salt diet may increase symptoms of asthma,[33] Burney[34] hypothesized that increased sodium intake may contribute to the increased morbidity and mortality of asthma observed in westernized cultures. Burney et al.[35] tested the hypothesis using the ecological data on asthma death rates and table salt purchases from regions in England and Wales. They found a strong correlation between table salt purchases and mortality because of asthma in men and in children of both sexes, but not in women. The suggestion from these data was that higher dietary sodium chloride may potentiate asthma severity. One explanation for the absence of an association in women was the possibility of the misclassification of women with bronchitis as asthmatic.

In a subsequent study, Burney et al.[35] conducted a cross sectional survey of the prevalence of asthma in rural and urban areas in the south of England. A random 20% of those men who replied, including all those who responded that they had symptoms of asthma, were tested for airway hyper-responsiveness with histamine challenge. A total of 205 men (aged 18-64 years) underwent bronchial reactivity testing, using the histamine challenge test, and of these 138 provided 24-h urine specimens. Regression analysis found increased 24-h urinary excretion of sodium, but not potassium, to be significantly associated with airway responsiveness to histamine. Thus, the authors concluded that a high sodium diet (HSD) may potentiate bronchial reactivity, although they were unable to exclude the possibility that the association may be a consequence of other unrecognized dietary or lifestyle factors associated with sodium intake. As the lower level of the sodium excretions presented in this study, 3841 mg/day, is typical for the Western diet, it is of some importance that airway responsiveness was increased across this already excessive range of dietary sodium intakes.

Schwartz and Weiss[36] used the information collected in the Second National Health and Nutrition Examination Survey to explore the potential relationships among the dietary factors and respiratory symptoms. The population examined was 9074 adults aged over 30 years old and dietary intake was derived from 24-h dietary recall questionnaires, yielding an estimated intake for sodium of 2640 mg/day and for potassium of 2334 mg/day. The sodium-potassium ratio was 1.25 on average. The analysis indicated that although neither sodium nor potassium in the diet was individually related to bronchitis or wheezing symptoms, the ratio of sodium to potassium was a significant predictor of bronchitis as reported by these adults. Although limited by the measurement error inherent to self-reported dietary estimates, these data do contribute to the body of evidence suggesting the dietary electrolytes may contribute to airway responsiveness.

Pistelli et al.[37] performed a cross sectional study in Italy among 2593 subjects aged 9-16 years. Questionnaires were used to determine the table salt use, asthma, and asthma symptoms such as wheezing and coughing. Personal table salt use was reported to be positively correlated with reported symptoms of asthma in boys but not in girls. A subset (n = 2020) of subjects underwent methacholine challenge and electrolyte analysis was conducted on 916 urine samples. Airway responsiveness was positively associated with urinary potassium excretion in boys, but not with urinary sodium excretion. Thus, while self-reported table salt use was related to symptoms of asthma, the more objective measure of urinary sodium concentration was not. There was no correlation in females between asthma symptoms and bronchial reactivity with either table salt usage or urine electrolyte concentration. This study used only a single sample of urine corrected for creatinine, and not a 24-h collection, which is a superior measure of sodium excretion and hence dietary intake. This study suggests that consumption of table salt or something associated with it may be associated with increased symptoms of asthma in boys.

Demissie et al.[38] surveyed children selecting 187 cases with a history of asthma or with EIB, along with 145 controls identified from a larger population of 1274 children in Montreal. The children were ranked for salt intake using an unvalidated food questionnaire, and children who had a FEV1 value >75% of their forced vital capacity (FVC) underwent methacholine challenge for airway responsiveness. The salt scores did not correlate with asthma (defined as a history of asthma or drop in FEV1 of >10% postexercise), but comparison of the lowest quartile with the highest quartile of salt intake demonstrated significantly higher airway responsiveness in the latter. Thus, despite the crude measurements used, there remained an increase in airway responsiveness with higher levels of salt intake.

Tribe et al.[39] carried out an investigation to study dietary sodium intake and bronchial reactivity, and how this effect may be mediated by cellular sodium transport mechanisms in men with asthma.[39] Asthmatic (n = 27) and non-asthmatic (n = 25) men were tested while on their usual diet. Blood leucocytes were used as a model for sodium transport mechanisms. Average sodium excretion was 3887 mg/day for those with asthma and 3818 mg/day for controls. Regression analysis revealed a significant positive relationship between 24 h sodium excretion and airway responsiveness. Additionally, the result from the leucocyte study suggested that a serum-borne factor found in asthmatic serum caused increased sodium influx into leucocytes and was related to the degree of hyper-responsiveness, but independent of the effect of 24-h sodium excretion on airway responsiveness. Hence, these data do support the concept of a positive association between the increased intake of dietary salt and airway responsiveness, while also suggesting that factors in the serum from men with asthma may be involved in both cellular sodium transport and bronchial hyper-responsiveness.

A case-control study of risk factors in the home environment for asthma in 154 children in Kenya identified supplemental salt intake as an independent risk factor for asthma, with a one SD in salt intake being associated with a 60% increase in risk of asthma.[40]

There have been four epidemiological studies, which have failed to demonstrate an association between dietary sodium and measures of asthma activity. The largest, by Britton et al.,[41] was a study designed to test the hypothesis that dietary sodium intake is an independent risk factor for bronchial hyper-reactivity in the general population. Airway responsiveness to methacholine, atopy, 24 h urinary sodium excretion, and self-reported smoking and symptom history were measured in a random sample of 1702 adults aged 18-70. The results showed no relation between the relative odds of hyper-reactivity to methacholine and 24 h urinary sodium excretion, either before or after adjusting for age, smoking, allergen skin weal diameter and gender. In addition, no association between 24 h sodium excretion and the magnitude of the mean allergen skin weal response or the PD20 value. The authors conclude that the findings do not support the hypothesis that a high dietary sodium intake is a risk factor for airway hyper-reactivity or atopic disease in the general adult population.

Deveroux et al.[42] used data from two epidemiological studies from the north of England, one of 1059 shipyard workers aged 16-27 years old, and a second of 587 men who lived in either rural or urban environments. Twenty-four hour urine samples were available for 22% and 40% of individuals who participated in the studies, respectively, and they demonstrated that there was no association between 24 h sodium excretion and airways responsiveness in either the shipyard workers or the subgroup of men who lived in a rural environment, but a positive association between 24 h sodium excretion and airways hyper-responsiveness in the subgroup of men who lived in an urban environment. One limitation of this study is the absence of data from up to 78% of individuals eligible to participate and the inability to exclude the possibility of response bias influencing the results.

Sparrow et al.[43] examined the methacholine airway responsiveness and the 24 h excretion of sodium and potassium. Methacholine airway responsiveness was examined among 273 male participants (age range 44-82 years) using 24 urinary excretion of Na+ and K+ as a surrogate for intake. A significant relationship between methacholine dose-response slope and potassium excretion was found. However, methacholine airway responsiveness was not correlated with sodium excretion.

Zoia et al.[44] sought to determine the relationship of sodium and potassium intake, assessed by means of a 7-day dietary questionnaire, with bronchial responsiveness in a sample of the general population. Two hundred and five participants completed the dietary and respiratory questionnaires and baseline pulmonary function, while 146 subjects underwent a histamine challenge test. These authors could not demonstrate a relationship between these dietary factors and bronchial responsiveness or respiratory symptoms, although this may be a consequence of the use of dietary questionnaires, which tend to be poor at measuring the sodium intake accurately.

These four studies[41,42,43,44] that have not demonstrated an association between sodium intake and asthma are difficult to reconcile with the studies that demonstrate an inverse relation reviewed earlier in this article. In particular, the study by Britton et al.[41] is a large study using the objective measures of both sodium intake and airway reactivity and provides a substantial challenge to the hypothesis that dietary sodium is associated with asthma in the general population. Possible explanations for the inconsistency of the data are that dietary factors may have a different effect in children and young adults, as the age of the individual is an important factor in determining the sensitivity to sodium, thus explaining why studies such as those of Britton et al.[41] and Sparrow et al.[43] that have examined relatively older populations do not observe an effect. Alternatively, dietary sodium may not have an effect on asthma in the general population.

Interventional Studies

The work by Stoesser and Cook[33] and the earlier epidemiological and cross-sectional studies[34,35] led to subsequent intervention studies testing the hypothesis that dietary salt was associated with asthma severity. Javaid et al.[45] performed an interventional study to examine the effect of changing dietary salt intake on bronchial reactivity as determined by a histamine challenge test in 10 volunteers with asthma and five controls. Baseline 24 h sodium excretion was 3588 mg/day in those individuals with asthma, and 2369 mg/day in the controls. The dietary salt was then increased for 4 weeks resulting in 24 h urinary sodium excretion of 4958 mg of sodium/day for those with asthma, and 4209 mg/day for the controls. The high salt intake significantly increased the bronchial reactivity when compared with the normal diet in asthmatics, but not for control subjects. This study adds support to the concept that elevating dietary salt from a moderate to a high level will increase airway responsiveness, in individuals with asthma but not healthy controls, although the relatively small numbers studied demand caution when interpreting the results because of the low power of this study to demonstrate an effect.

Burney et al.[46] followed up their original observations with an interventional study using a randomized double-blind cross-over study design comparing the supplementation of the normal diet with 1840 mg sodium per day with placebo supplementation in 36 asthmatic patients on the LSD. Prior to implementation of the LSD, urinary excretion of sodium was 2438 mg/day suggesting that this was a population already consuming a relatively salt-free diet. The LSD and placebo supplements resulted in a decrease of 24 h urinary sodium excretion of 736 mg/day in men and by 805 mg/day in women, while with the LSD and sodium supplementation, sodium excretion increased slightly above the baseline. Compared with baseline, there was a decrease in airway reactivity as measured by histamine challenge in men while on the LSD and taking placebo and an increase after supplementing the LSD with replacement salt. The dose of histamine causing a fall of 20% in FEV1 (PD20) was 1.51 doubling doses lower (i.e. increased airway responsiveness) when taking the sodium supplementation regimen compared with when taking placebo (LSD). This effect was not observed in asthmatic women. Thus, in asthmatic men, lowering dietary salt intake for 2 weeks reduced their airway hyper-responsiveness. The fact that airway hyper-responsiveness did not change in women with asthma after dietary sodium manipulation was consistent with the researchers' earlier epidemiological finding,[34] although no mechanism is known that explains the possible gender differential in airway responsiveness to dietary salt manipulation.

Carey et al.[47] studied 27 asthmatic men receiving 5 weeks of 4600 mg of slow sodium release capsules or placebo capsules daily in a random order (double-blind, cross-over design), while maintaining the LSD (1840 mg/day of sodium). Pulmonary function testing and methacholine challenge was performed at baseline, then at the end of each 5-week period. Daily peak expiratory flow rates (PEFRs) were recorded by the patients, as was medication use. On the normal diet, sodium excretion was 3657 mg/day. The LSD plus placebo produced a 24 h excretion of sodium of 2029 mg/day; and the LSD plus sodium supplement yielded 6716 mg of sodium per day. The LSD plus placebo was compared with the LSD plus sodium and was associated with lower methacholine reactivity (a decrease of 0.73 doubling doses), deceased bronchodilator usage, with higher PEFRs (5-8%) and FEV1 values (210 ml). Thus, lower salt intakes were associated with improved pulmonary function, reduced asthmatic symptoms and medication use and reduced airway hyper-responsiveness. This study only used male subjects, so no conclusion with regard to the effect of sodium manipulation in females with asthma can be drawn.

Similarly, Medici et al.[48] studied the effect of dietary salt reduction and supplementation on severity of asthma, and in addition examined the possibility that the chloride ion has an active role in the effect of salt in modifying asthma severity. Using a cross-over design, 14 asthmatics (nine men and five women) were placed on the LSD (5-6 g/d of salt; 1978-2369 mg of sodium) for 2 weeks. Subjects then consumed nine capsules throughout the day containing 1 g of salt or placebo for the first 3 weeks, and then crossed over to the second intervention (salt or placebo) treatments for the second 3 weeks. After this, participants then received 3 weeks of sodium citrate as the supplement (with equivalent sodium to that received with the previous salt supplementation). Finally, subjects returned to their usual diet and were followed for 3 weeks. Medication use and peak expiratory flows (PEF) in the morning, noon and evening were recorded daily. Twenty-four hour urine collections documented electrolyte consumption. Laboratory pulmonary function testing and methacholine challenge were performed at regular intervals throughout the study. The mean values for sodium and chloride consumption in this study were 1817 mg sodium, 2982 mg chloride on the LSD; 3151 mg sodium, 4651 mg chloride on the high salt diet; 3083 mg sodium, 3160 mg chloride on the sodium citrate diet; and 2530 mg sodium, 3905 mg chloride on the patients' usual diet. Patients reported an increase in increased inhaled steroid use and a decrease in PEFR on the high salt diet, but changes in dietary salt had no demonstrable effect on airway responsiveness as measured by methacholine challenge. Sodium citrate loading did not alter these outcomes, suggesting that the sodium ion is an important contributor to these observed effects of salt loading. It is important to note that normal asthma medications were continued during the study and the medication including inhaled corticosteroids was adjusted if the asthma deteriorated as assessed by an increase in asthma symptoms or a decline in PEFR declined. Thus, it is difficult to interpret the data on airway responsiveness, as titration of the medications potentially would mask any response.

Lieberman et al.[49] examined the hypothesis that the amount of daily salt intake influences the severity of asthma as measured by PEF and the variation in PEF during the day. Seventeen asthmatics (nine men and eight women, 27-62 yeas of age) were observed on their normal diet, after 2 weeks of the LSD, and after 2 weeks of a high salt diet plus daily salt tablets, and PEF monitored at home. Normal diets resulted in sodium excretion of 3381 mg/day; LSD, 1932 mg/day; and high salt diet, 4623 mg/day. There was no effect on either PEF or PEF variability. While subject numbers were low and hence the study was relatively underpowered, these data do not support the general concept of a relationship between the sodium intake and asthma severity. However, airway responsiveness was not measured and the detail that 10 subjects were on daily oral theophylline which improves asthma control would also reduce the likelihood of seeing a beneficial response.

In a recent Cochrane Database Systematic Review, Arden et al.[50] assessed the effect of dietary sodium reduction in patents with asthma. Only six studies fulfilled the inclusion criteria of being randomized-controlled trials, all of which are also reviewed in detail within this present review.[46,47,48,49,51,52] A meta-analysis of selected data from four of these studies,[48,49,51,52] along with individual study analysis,[46,47] indicated that there was a pattern suggestive of a small improvement of pulmonary function with a salt restrictive diet and a small reduction in bronchodilator use. Based on the available evidence at the time of the review and considering the small sample size of these studies, the authors decided that it was not possible to conclude whether dietary sodium reduction is beneficial as a treatment for asthma.

Collectively, the studies to date investigating the potential relationship between dietary sodium and the severity of asthma or airway hyper-responsiveness have provided support for the hypothesis that increased dietary intake of sodium may increase the severity of disease in those with asthma. A large randomized-controlled clinical trail is warranted to fully address this issue and should include individuals with well characterized asthma, data on baseline diet, and be sufficiently powered to permit measurement of both physiological outcomes such as lung function and bronchial reactivity, as well as clinically important measures including the daily symptoms score and medication use.

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