1. INTRODUCTION

Salt has been used from centuries as a food ingredient and a precious substance to preserve foods warranting their storage in case of scarcity. For this reason, it has been also considered a currency and taxed in many countries both in Europe and in Orient, as, for example, proved by the word “salary” deriving from this use. Salt remained a primary means of food preservation until the late 19th and 20th Centuries, when other methods, such as refrigeration and freezing, were introduced. Although actually consumers consider salt as a substance that improves taste and flavor, its preservative properties are still used. The consumption of high amounts of salt is popular in oriental countries, as, for example, in China and Japan, where salt is added to many aliments and is also involved in the related side effects.¹

In the recent years, many studies have correlated the excess of salt intake with an increased rate of hypertension and cardio‐cerebrovascular accidents,² therefore the World Health Organization (WHO) recommends for adults a sodium consumption <2 grams/day (equivalent to a salt intake <5 g/d) as first‐line intervention to reduce blood pressure values and risk of strokes and cardiovascular diseases.³

The recent study of Iida et al⁴ evaluated the association between estimated salt intake from spot urine sample and body weight with blood pressure in the very elderly population (age ≥ 75 years), living in a Japanese community. From this study, the authors confirmed a higher estimated salt intake than those recommended by WHO and by the Japanese Ministry of Health and Welfare⁵ even in this very elderly population. Moreover, the increased systolic blood pressure was associated to both salt intake and body weight, while increased diastolic blood pressure was associated only with body weight.

2. THE ESTIMATION OF SALT INTAKE BY SPOT URINE SAMPLE

The gold standard for assessment of salt intake is the collection of 24‐hour urine,⁶ but recently many authors proposed the use of spot urine samples, which are easily collected and avoid the inaccuracy of collection and losses.⁷ Iida et al⁴ calculated the daily salt intake using the Tanaka method,⁸ through the calculation of 24‐hour sodium and creatinine levels determined from spot urine samples collected in the morning. This method has different limitations, since it represents the sodium ingestion in the short period preceding the collection and is influenced by individual variability depending on salt and water intake in the previous hours, several hormonal and non‐hormonal factors involved in sodium concentration.⁹ Validation studies are recommended to identify the most suitable prediction equation in different population groups,⁶ and the previous studies concluded that the prediction equations based on single spot urine samples are inadequate for the estimation of an individual's sodium intake. However, several large‐scale epidemiological and observational studies have used the estimation of salt intake by spot urine sample and the Tanaka method is recommended by Japanese hypertension guidelines. Finally, we believe that in studies with very elderly subjects the use of a spot urine is actually the most appropriate method to estimate salt intake, considering the difficulty to collect 24‐hour urine due to frequent urine incontinence.

The study of Iida et al⁴ evidenced an increased estimated salt intake in the evaluated very elderly population, consistent with other studies and confirming a much higher sodium intake in Japan than in USA and in Europe. It is worth of note that the life expectation and the number of centenarians are higher in Japan than in many other countries. From these observations, some genetic or epigenetic factors may be involved in the discrepancy between the incidence of hypertension and the life expectance in Japan.

3. THE INFLUENCE OF TREATMENT OF HYPERTENSION ON ESTIMATION OF SALT INTAKE

The most important limitation to the use of the spot urine sample is the antihypertensive drugs. Some previous studies did not consider the detailed medication history and could not adjust their data for the use of diuretics.¹⁰ Diuretics, which can affect sodium excretion, are widely used to treat hypertension particularly in elderly. They have different mechanisms of action on sodium metabolism. Furosemide and thiazide increase sodium and potassium excretion, while mineralocorticoid receptor (MR) blockers impair the effect of aldosterone leading to sodium excretion and potassium reabsorption. All these drugs have a dual effect on the cardiovascular risk, since they induce volume depletion and blood pressure decrease, but even a secondary aldosteronism.¹¹ It is well known the role of aldosterone as cardiovascular risk factor and only MR blockers can blunt its proinflammatory and profibrotic effects, preventing and reducing the cardiovascular events even in patients with normal aldosterone values.¹²

Many other antihypertensive drugs are involved in sodium metabolism, such as ACE‐inhibitors and angiotensin II type 1 receptor blockers. These drugs decrease aldosterone secretion impairing the synthesis of angiotensin II, and this effect is consistent with the important role of these drugs in reducing the cardiovascular risk. However, the calculation of the salt intake using spot urine sample or 24‐hour urine could be disturbed. Beta‐blockers can also decrease renin and aldosterone, by a direct effect on renin secretion. The only drugs that do not significantly affect the renin angiotensin aldosterone system are calcium antagonists and alpha‐blockers, and for this reason, they are recommended as medications to control hypertension in case of screening test and further evaluations for suspected primary aldosteronism (PA).¹³

Finally, a previous study by Won et al¹⁴ showed that 24‐hour urine sodium excretion was positively associated with the prevalence of metabolic syndrome in subjects not on antihypertensive medication, while the association was not evident in subjects on antihypertensive medication. The authors explained this discrepancy with the attention of hypertensive patients in the limitation of salt intake, in body weight and other lifestyle measures and this could be a confounding factor in the evaluation of association between 24‐hour urine sodium excretion and the prevalence of metabolic syndrome.

4. HORMONAL REGULATION OF VOLUME AND ELECTROLYTE BALANCE

A fundamental role in the regulation of volume and electrolyte is played by aldosterone, ADH, and other natriuretic factors. Aldosterone is regulated by renin, which is regulated by the concentration of sodium at the level of macula densa and by the volume in juxtaglomerular apparatus. On the other hand, aldosterone regulates the sodium, potassium, and blood pressure binding to MR in kidney and in the other target tissues. When sodium intake is high, mechanisms of defense are activated as the block of renin secretion by the juxtaglomerular apparatus, leading to a decrease of aldosterone. It is interesting to note that the excess of salt intake decreases aldosterone until a certain level and a further decrease of aldosterone is blocked. A block of aldosterone effector mechanism in the classical target tissues appears also in PA, the so‐called “escape phenomenon,” due to the decreased sodium reabsorption of nephron segments other than those of aldosterone action.¹⁵ This compensatory mechanism involves not only ADH and natriuretic peptides, but also the saturation of MR at the level of kidney and other target tissues, as demonstrated in down‐regulation of MR in mononuclear leukocytes in PA.¹⁶

The important role of potassium in the sodium regulation must be also considered. Very low potassium concentrations, as in PA or in chronic administration of furosemide, can impair the secretion of aldosterone at the level of adrenal zona glomerulosa cells, and in the diagnosis of PA, the administration of potassium can sometimes better evidence an increase of aldosterone‐renin ratio. The excess of cortisol, such as in Cushing's syndrome or corticosteroid intake, can also regulate the sodium and volume balance, inducing a pseudo‐hyperaldosteronism, due to the saturation of the 11‐hydroxysteroid dehydrogenase type 2.¹⁷ This enzyme is located at the level of renal tubular cells and other classical target tissues of aldosterone and allows aldosterone to bind MR, inactivating cortisol in cortisone.

Plasma volume and sodium are also regulated by water intake. Excess of water can suppress renin, aldosterone, and ADH and decrease plasma and urinary osmolality due to volume dilution; however, in this case, the estimation of sodium excretion cannot be considered a marker of sodium intake.¹

5. CONCLUSIONS

From all these considerations, it is very important to perform an accurate history of the patient in situations of altered homeostasis of water and electrolytes, considering the possible interference of treatments for a correct estimation of salt intake, particularly in patients with hypertension and metabolic syndrome. Genetic and epigenetic factors could be implicated both in the regulation of sodium intake and sodium metabolism, but it is important to prescribe lifestyle modifications to counteract the genetic predisposition to hypertension and metabolic syndrome.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

REFERENCES