Dietary Sodium Intake and Asthma: An Epidemiological and Clinical Review

T. D. Mickleborough; A. Fogarty


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

In This Article

Dietary Sodium and Exercise-Induced Bronchoconstriction

Exercise provides a safe and easily controlled challenge to the airways that permits the evaluation of potential interventions such as the effects of dietary modulation on asthma and airway hyper-responsiveness. All the subjects in the following studies had mild-to-moderate persistent asthma and exhibited EIB as shown by a >10% decrease in post exercise FEV1 compared with pre-exercise values.

To assess the effect of dietary sodium manipulation on the severity of EIB, an initial study was conducted by Mickleborough et al.[53] and utilized a double-blind randomized crossover study design. Fifteen individuals with asthma entered the study on their normal salt diet (NSD), and then were placed on either LSD or HSD for 2 weeks. A 1-week washout period on the NSD was included before crossing over to the second treatment period of 2 weeks. Pre- and post exercise pulmonary function tests were performed following each treatment period. For all three diet treatments, 24-h urinary sodium excretions were significantly different (NSD = 3630 mg/day; LSD = 958 mg/day; HSD = 8133 mg/day). Comparing the change in lung function 5 min after an exercise challenge, FVC and FEV1 significantly improved by 0.95 L and 0.4 L on the LSD, whereas the HSD induced significant reductions of 0.22 L and 0.37 L in FVC and FEV1, respectively. The data demonstrated for the first time that 2 weeks of dietary salt loading worsened and 2 weeks of salt restriction improved the post exercise pulmonary function in volunteers with EIB. In addition, the LSD improved and the HSD exacerbated pulmonary function during exercise in EIB subjects.[52] Specifically, arterial oxygen saturation during exercise was improved by reducing the dietary sodium and worsened by increasing the dietary sodium. The pattern of ventilation during exercise differed with diet, with the HSD resulting in a higher tidal volume and lower breathing frequency selection; the LSD reversed this pattern, with a lower tidal volume and higher breathing frequency.

Gotshall et al.,[51] in a follow-up study, conducted a double-blind randomized crossover study to assess the effect of 2 weeks of dietary salt loading and restriction on eight individuals with asthma and EIB, plus eight non-asthmatic controls. Otherwise, study conditions were identical to the previous study.[53] Pulmonary function was assessed pre- and post exercise and before and after each treatment period. Diet had no effect on pre-exercise pulmonary function values in either group and had no effect on post exercise pulmonary function values in control subjects. However, the LSD improved and the HSD worsened post exercise pulmonary function values in EIB subjects. FEV1 decreased by 14% on the LSD, 20% on the NSD and 24% on the HSD at 15 min post exercise. Dietary goals were achieved as urinary sodium excretion fell significantly on the LSD (1335 mg/day) and increased significantly on the HSD (6750 mg/day).

Recently, Gotshall et al.[54] conducted a study to determine whether a shorter regimen of dietary sodium restriction (1 week) would prove as effective as 2 weeks of sodium restriction in reducing the severity of EIB. Ten individuals with EIB and 10 controls without EIB participated in a randomized double-blind cross-over trial and were placed either on approximately 1500 mg of sodium for 2 weeks, which constituted the LSD or on their NSD. At baseline (NSD), the EIB subjects demonstrated significant reductions in FEV1 of –27%, –24% and –20% at 1, 5, and 15 min post exercise, respectively. However, after 1 week on the LSD, post exercise FEV1 improved significantly to –4.5%, –8.9% and –7.63% and after 2 weeks on the LSD to –3.2%, –8.9% and –7.7% at 1, 5, 15 min post exercise, respectively. Thus, the LSD noticeably reduced the severity of EIB and had a similar effect at both 1 and 2 weeks.

As salt comprises both sodium and chloride, it is possible that the anion, chloride, plays an active role in the effect of salt on EIB. In hypertension research, there have been many studies implicating the chloride ion as the main contributor to elevated blood pressure during dietary salt loading. For example, sodium loading with anions other than chloride has failed to produce the elevated blood pressures in models of salt-sensitive hypertension.[55,56] Hence, Mickleborough et al.[57] evaluated the influence of low and high chloride diets on the severity of EIB. The study design and protocol were conducted in a similar fashion as the study performed by Gotshall et al.[51] with the only difference being that upon entering the study on the NSD, all participants (EIB, n = 8, and control, n = 8) were either placed on the LSD (low sodium, low chloride) for 2 weeks or a sodium bicarbonate (NaHCO3) diet (high sodium, low chloride) for 2 weeks. The data confirmed earlier observations[51,52,53] that the LSD significantly blunted the decline in post exercise pulmonary function in EIB subjects without any effect in control subjects. Additionally, the data indicated that dietary chloride reduction coupled with dietary sodium elevation (NaHCO3 loading) also attenuated the decrement in post exercise pulmonary function in EIB subjects, but not to the extent of the LSD (low dietary sodium and chloride). FEV1 fell 7% on the LSD, 14% on the NaHCO3 diet and 19% on the NSD. Urinary excretion of sodium was 1761, 3477 and 6266 mg/day on the LSD, NSD and NaHCO3 diet, respectively. There was no significant difference in urinary chloride excretion between the LSD (3043 mg/day) and NaHCO3 diet (2722 mg/day). These data suggest that both the sodium and chloride ion may contribute to the deterioration of the severity of EIB seen after a NSD or HSD.

In an attempt to delineate a possible mechanism by which dietary salt loading might exacerbate EIB, Mickleborough et al.[58] used the guinea pig model for EIB. The guinea pig manifests dry-gas hyperpnea-induced airway obstruction (HIAO) that parallels the response seen in human subjects with EIB.[59,60] As it has been suggested that EIB and HIAO in guinea pigs are mediated by similar mechanisms,[59,60] the purpose of the study conducted by Mickleborough et al.[58] was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, in order to delineate a possible mechanism by which dietary salt may exert an effect on airway responsiveness, the potential pathway of action of dietary salt was investigated by blocking leucotriene (LT) production during HIAO in guinea pigs. Thirty-two guinea pigs were split into two groups. One group (n = 16) of animals consumed the NSD (0.75% salt; which is the normal salt content of guinea pig feed) for 2 weeks, whereas the other group of animals (n = 16) ingested the HSD (2% salt). At the end of each treatment period, the animals were anaesthetised, cannulated, tracheotomised and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered masoprocol (nordihydroguaiaretic acid), which is an LT biosynthesis and lipoxygenase inhibitor. The HSD elicited significantly higher airway inspiratory pressures (Ptr) than the NSD post challenge. However, following the infusion of masoprocol and a second hyperpnea challenge, Ptr was significantly reduced in both diet groups, although the HSD continued to be associated with a higher Ptr than the NSD. Urinary LTE4 excretion significantly increased in the HSD group compared with the NSD group. This novel study demonstrated, for the first time, that elevated dietary salt increased the HIAO response compared with the NSD, and that this effect may be mediated by changes in LT metabolism. The potential interactions of dietary salt and LT production and release in this animal model have yet to be determined. However, a major limitation in this study is that urinary LTE4 excretion may not be reflective of airway cell activity, but in fact be linked to the influence of dietary salt on the kidneys via changes in osmoreceptor activity or the rennin-angiotensin system during exercise, as the kidneys are rich sources of LTs and prostaglandins.

Recently, Mickleborough et al.,[61] using a double-blind placebo-controlled randomized crossover design, attempted to determine a possible mechanism by which dietary salt modification may alter EIB in 24 asthmatic patients. The study design was identical to the previous study performed by Gotshall et al.[51] All subjects were required to consume a base diet of 1500 mg/day of sodium, and approximately 2250 mg/day of chloride, which was provided by a menu plan, whether on the LSD or HSD. For the HSD, the base diet was supplemented with ten 1-g salt capsules per day comprising 4000 mg/day of sodium, and approximately 6000 mg/day of chloride (169 mmol/day). For the LSD, the base diet was supplemented in the same manner but with placebo (sucrose) tablets.

This study[61] demonstrated for the first time that modifying dietary salt intake for 2 weeks alters airway inflammation, diffusion capacity of the lung (DLCO), and confirms previous observations that altering dietary salt intake can modify the severity of EIA[51,57] with a concomitant reduction in bronchodilator drug use. Induced sputum differential eosinophil and neutrophil cell counts, eosinophil cationic protein, proinflammatory cytokines interleukin (IL)-1β, IL-8 and eicosanoids LTC4-E4, LTB4 and prostaglandin D2 were significantly higher following exercise on the NSD and HSD compared with the LSD. In addition, the NSD and HSD caused a significant reduction in DLCO and an increase in pulmonary capillary blood volume (VC), while the LSD produced a significant increase in DLCO and diminution in VC. One potential mechanism is suggested by the observation that dietary salt manipulation modified the induced sputum supernatant IL-1β and IL-8 concentration following the exercise, both cytokines that are associated with neutrophilic inflammation,[62] although asthma is characteristically associated with airway eosinophilia. This may be a consequence of hyperosmolarity, which has been shown to stimulate IL-8 production in human bronchial epithelial cells in vitro.[62] Alternatively, as the human airway mucosa is a semi-permeable membrane which permits osmotic equilibration, it may be hypothesised that dietary salt loading increases airway osmolarity and enhances the release of other proinflammatory mediators including the prostaglandins and LTs.

In summary, these series of studies have provided convincing evidence that salt intake is inversely related with the severity of the bronchoconstrictor response to exercise in asthmatic subjects with EIB. While there are large variations in individual responses, the LSD (approximately 1500 mg sodium per day) reduces the severity of EIB. As most of the data of the association between dietary sodium and EIB have been published by one research team (led by one of the authors of this article), there is a need for similar studies in other populations to see if this effect is reproducible elsewhere.


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