4.1. Sulphate mineral waters in gastroenteric disorders

Sulphate mineral waters, mainly magnesium sulphate-rich and sodium sulphate-rich, have a purgative-laxative function, as a consequence of a hypertonia. They rapidly transit through the stomach and arrive in the gut where they recall the presence of water. In this way, faecal excretion is facilitated with an increase in volume and a marked decrease in consistency and improvement on both the number of evacuations and colon motility as reported by Dupont et al.9 in a randomized double-blind clinical trial involving women with functional constipation. In particular, these authors have demonstrated that daily consumption of magnesium sulphate-rich natural mineral water was more effective than low-mineral water in reducing constipation.

Ikarashi et al.10 demonstrated through an in vitro study that magnesium sulphate might increase the aquaporin 3 (AQP3) expression levels and change the osmotic pressure in the colon. Bothe et al. have recently shown that daily consumption of mineral waters, rich in magnesium sulphate and in sodium sulphate, is useful for healthy digestion improving constipation symptoms, overall bowel movements and stool consistency.11

A meta-analysis demonstrated that in European populations, in particular in Scandinavians, higher levels of magnesium in drinking water might reduce the risk of mortality due to coronary heart diseases.12

Chloride sulphate waters stimulate intestinal motility and are administered against chronic constipation and other digestive and hepatic biliary disorders.5

Sulphate bicarbonate-calcium-magnesiac mineral waters, administered as hydropinotherapy, are useful against disorders of the biliary tract; these waters are particularly efficacious thanks to anions that exert choleresis and cholagogue actions, thus helping in removing gallbladder hypomotility and correcting the tendency to gallstones.2,13

Corradini et al.14 have shown a beneficial effect of the hydropinic treatment with sulphate-bicarbonate-calcium mineral waters in reducing the risk of biliary calculi and favoring weight control. Moreover, the same spa treatment with sulphate-calcium mineral waters may effectively normalize the echoscopy picture and the motor function of stomach and gallbladder.15

Fraioli et al.16 underscore efficacy of waters rich in sulphate and bicarbonate in lithogenic bile, because of their diluting and washing activity. In addition, they show a positive effect in the treatment of biliary dyskinesia due to the release of cholecystokinin (CCK) and a consequent gallbladder contraction and Oddi sphincter relaxation. Pharmacological studies1,17,18 have shown that magnesium participates in the synthesis of digestive enzymes and hormones such as CCK.

Magnesium, thanks to its inhibitory action on the gastric acid secretion, competes with calcium. This confirms the clinical evidence that calcium-sulphate waters (poor in magnesium) have hyper-secretive action and are not well tolerated in patients suffering from gastro-duodenal ulcer and hyper-secretive gastropathies, whereas they are indicated in digestive insufficiencies characterized by gastric hypo-secretion and hypo-motility with or without a spastic component.

Several mineral waters have a trophic, antitoxic and metabolic action on the liver. For example, it was observed that a reduction in steatosis, experimentally induced by carbon tetrachloride (CCl4), occurred as a consequence of the assumption of bicarbonate-sulphate-alkaline-earth waters.1 As a matter of the fact, Montecatini (Italy) spa mineral water, classified as sodium-chloride sulphate alkaline and administered through hydropinotherapy, has been used for centuries to treat pathologies affecting liver, stomach and guts. Similarly, the sodium chloride-sulphate mineral waters improve the biliary function by choleretic and cholagogue actions.1 Studies performed by using radiological and ecographic screening have highlighted significative volume variations of gallbladder after assumption of sulphate waters.1

The intake of sulphate sodium-chloride mineral waters activates carbohydrate metabolism. Indeed, it has been demonstrated in animal models that such kind of mineral water enhances resistance to stressful factors and may promote trophic effects of insulin and gastrin with significant reduction in peptic ulcer size.19,20

Magnesic-sulphate-sulphurous mineral waters have been shown to have a very good hypocholesterolaemic activity and protective effect against oxidative lipid damage.4,21

Studies investigating the effects of Montecatini spa mineral waters on bile acid extraction and lipid and apolipoprotein serum levels suggested that a treatment with salt-rich spring waters reduces serum LDL levels in subjects with mild hypercholesterolaemia, through a mechanism of increased excretion of the faecal bile acid sterols.4

Sulphate is also an important nutrient in foetal growth and development, particularly in late gestation when foetal demand for sulphate is high. For this reason sulphate mineral waters may be a useful alternative for diet of pregnant women.2,22

4.2. Sulphate mineral waters in musculoskeletal disorders

Sulphate mineral waters administered by using balneotherapy, mud therapy and mud-balneotherapy have shown efficacy in the treatment of various chronic diseases of the locomotor system.23,24

Epidemiological data show that patients suffering from osteoarthritis are among the most frequent users of spa treatments, followed by patients with respiratory disorders.25

It has been demonstrated that mud maturated with sodium-chloride sulphate mineral water exerts anti-inflammatory activity. Schettino and coworkers26 showed that the anti-inflammatory activity of this mud is characterized by a 30% reduction of the edema induced by carragenin. Moreover, other authors27,28 have underlined the benefits of a cycle of mud-balneotherapy with sodium-chloride sulphate mineral water in patients affected by gonarthrosis, one of the main causes of movement impairment in elderly. These benefits encompass a significative reduction of severity and frequency of pain symptomathology and Lequesne index, with a concomitant reduction of disability.28 Importantly, a therapeutic synergism is observed when a pharmacological treatment is associated to mud-balneotherapy. This aspect prompts the need for a multidisciplinary approach to treat chronic diseases such as gonarthrosis.27 Fioravanti et al. have performed a randomized, single-blind controlled trial in which the effects of mud-bath therapy were compared to usual treatment in patients with bilateral knee osteoarthritis, showing improvement of pain, WOMAC index and quality of life in subjects who have undergone spa treatment.29

Notably, the cost effectiveness of the mud-bath therapy used in association with usual treatment in such a clinical setting was demonstrated by medical assessment and the measurement of quality-adjusted life years (QALYs). Indeed, a favorable economic profile of a single mud-bath cycle with sulphate mineral waters provided a significant reduction of hospitalization and average costs per patient for pharmacologic therapies.30

A prospective randomized, single blind-controlled, trial showed that sulphate mud-balneotherapy modifies adiponectin and resistin serum levels but not the circulating levels of visfatin. In view of the recent evidences concerning the involvement of adiponectin and resistin in the pathogenesis of osteoarthritis, the decrease of these adipokines after mud-balneotherapy may contribute to delay the progression of such diseases.31 In the osteoarthritis, an important role is also played also by release of free radical species produced by sinovial inflammatory cells and by the chondrocytes.32 In this context mud-balneotherapy seems to have an antioxidant role as shown by several studies.33,34 For instance, mud-balneotherapy with carbonate-sulphate alkaline mineral waters reduces the levels of oxygen free radicals in patients with rheumatological chronic diseases.35

Fortunati et al.,25 have shown that balneotherapy and mud therapy induce pain relief and improve the muscular function as well as quality of life (QoL) in patients with osteoarthritis and, importantly, clinical efficacy has been proven also to persist after treatment. Scalabrino et al. have demonstrated increase of peptides and opioid hormones after a single mud-bath treatment with alkaline-saline-sulphate waters.36

The efficacy of balneotherapy with mineral water rich in sodium, carbonates and sulphates was also demonstrated in patients affected by fibromyalgia, where a decrease of pain intensity and depression level together with a marked improvement of the functional capacity were described.37, 38, 39

4.3. Sulphate mineral waters in skin disorders

Comé, one of the main representatives of the thermalism in dermatology, introduced the term of “mineral eudermic water” to identify waters able to provide the organism with all factors necessary for nutritional, eutrophic and rehydrating action. When we consider the effect of mineral waters, including sulphate mineral waters, in stimulating skin turnover and toxins removal, it is quite easy to understand the role of spa therapy for treatment of dermatological diseases such as psoriasis, atopic dermatitis and acne. From the biochemical point of view, several aspects have been underlined. Magnesium, for example, has a central role in the growth and differentiation of keratinocytes and it is responsible for helping skin in preserving the lack of water, thus acting as a natural moisturizing agent. These effects are very useful to treat and manage pathologies such as psoriasis and atopic dermatitis.40,41

Hercogova et al.42 have shown anti-inflammatory effects of sodium-chloride sulphate mineral waters on human skin during inflammatory reactions caused by the direct application of irritant chemicals.

An antioxidant effect of sulphate-rich waters has also been reported by Bajgai et al.43 who showed a significant improvement of the redox balance in SKH1 hairless mice with atopic dermatitis induced by the application of 2,4-dinitrochlorobenzene (DNCB).43

Tsoureli-Nikita et al.44 have demonstrated a potential anti-inflammatory effect of balneotherapy with sodium-chloride sulphate mineral water in patients with plaque psoriasis obtained by a significant decrease in Psoriasis Area and Severity Index (PASI index). Moreover, balneotherapy with carbonate-sulphate-calcium mineral waters allows softening injuries and removing the scales, alongside with an improvement of the plaque aspect itself.

An antioxidant activity of carbonate-sulphate alkaline waters used either in mud-balneotherapy or speleotherapy (exposure to mineral waters in thermal caves) has been also demonstrated.35,45 This is very important when we consider the role played by free radical species in skin aging and in the pathogenesis of several dermatological diseases such as psoriasis, a condition in which a correlation between oxidative stress and inflammation has been provided.46

The evidence of an oxidant environment in psoriasis, both at the systemic and local levels, has been extensively reported in literature. This condition is produced by a massive release of Reactive Oxygen Species (ROS) from immune system cells, particularly neutrophils; it is typical of inflammatory processes and mediated by cytokines (TNFα, in particular).47 For instance, Joly et al.48 demonstrated the positive effects of sulphate carbonate-calcium-magnesium rich-waters in preventing ROS induced damage. Moreover, the plasmatic levels of nitric oxide (NO) and malondialdehyde (MDA), whose production in strictly linked to ROS increase, are also significantly higher in patients suffering from psoriasis than in healthy volunteers.49

Altogether, these evidences suggested a key role played by modifications of the normal redox balance in psoriasis pathogenesis.46 Therefore, spa therapies, which have been reported to exert anti-oxidant activities,35,50 could be expected to have beneficial effects in the treatment of plaque psoriasis.

An in vivo study performed on a psoriasis murine model51 showed that, compared to administration of distilled water, balneotherapy with sulphate-hydrogen carbonate-thiols rich mineral waters is effective in producing immunomodulatory effects, and lead to a marked reduction of cytokines involved in psoriasis and skin erythema pathogenesis, including IL-23, IL-17, IL4 and IL5. Based on this evidence, the authors suggested that spa balneotherapy is considered an effective and safe treatment for mild-moderate plaque psoriasis. Therefore, spa balneotherapy in dermatological care might be used alone, allowing patients to stop the drugs assumption at least for a short period of time, or as complementary therapy of conventional medical approach.52,53

It has been observed by Ricci et al.54 that balneotherapy with bicarbonate-sulphate-rich mineral waters ameliorate the wounds of patients with atopic dermatitis thanks to their moisturizing and soothing effect induced by the buffering-alkalizing action of bicarbonate anion.

Spa mineral waters could also have positive effects after chemical peeling procedures. Indeed, the main undesired effect of chemical peeling is local inflammation, which is generally prevented or attenuated by using of antibiotics or topical steroids. Unfortunately, since chemical peeling reduces skin corneal layers and increases skin permeability these drugs might have toxic effects. The ability of bicarbonate-sulphate-rich mineral waters to mitigate inflammatory processes produced by a 24-h treatment with an aggressive chemical exfoliating agent (trichloroacetic acid-TCA) has been demonstrated in an in vivo study.55

Also Faga et al.56 using an animal model showed that bicarbonate-calcium-magnesium-rich mineral waters improve skin regeneration. Moreover, Casas and colleagues57 described the positive effects of such spa mineral waters on the skin of patients affected by chronic dermatosis. Concomitantly, a sensible decrease of inflammation and a reduced colonization by Staphylococcus aureus, whose toxins can induce atopic dermatitis and psoriasis, were described.56

4.4. Sulphate mineral waters in respiratory disorders

SMWs administered through inhaled or irrigation crenotherapy thanks to specific effect of their various active components can be considered a valid therapeutic option in several chronic respiratory diseases.

Antiseptic action of sodium chloride (NaCl), increase of the metabolic and cellular activity of iodine (I), analgesic and sedative effects on mucosa induced by bromide (Br) and calcium (Ca), increase of secretory IgA activity produced by sulfur (S) have been largely recognized.

Administration methods are also important. For example, direct vapor-jet inhalation is indicated for chronic diseases of the upper respiratory tract such as rhinosinusitis, pharyngitis and laryngitis. In this method inhaled particles of about 100 μm in size exert a mechanical detergent action on the respiratory mucosa. Aerosol method (particles under 2 μm in diameter) delivers the active components of the waters to the lower respiratory tract, as far as the alveoli. Aerosol therapy is therefore indicated in chronic bronchitis (e.g., smokers' cough) and chronic obstructive pulmonary disease (COPD). Nebulization (particles of 10 μm) is utilized in cases of absent or insufficient mucosal secretion (bronchial and lung disease). In cases of rhinogenic deafness caused by the presence of catarrh in the middle ear, tubo-tympanic insufflation is used to push up the water vapor to the affected areas. Moreover, as inhalation treatments stimulate the body's overall immune defense mechanisms, they are also particularly indicated in the treatment of childhood diseases.

Passali et al.58 showed that inhalation treatment with bicarbonate-sulphate-alkaline-earth carbonated waters is beneficial against catarrhal conditions of the upper respiratory tract.

Ricevuti et al.59 showed particular benefits on the homeostasis of the alveolar surfactant compromised by tobacco smoke in rats exposed to inhalation crenotherapy with sulphate mineral waters. It has also been documented an anti-reactive action of magnesium, generally present in sulphate mineral waters, which is responsible for reduction of bronchial hyperactivity at different stimuli.60

Cantone et al.61 have shown that spa treatment with sodium-chloride sulphate waters results in a statistically significant improvement of ciliary motility in elderly subjects suffering from chronic rhinosinusitis.

Passariello et al.62 demonstrated that spa therapy consisting of sulphate-sodium chloride mineral water inhalations by aerosol (15min/day) induced in pediatric patients suffering from chronic rhinosinusitis a significant improvement of symptoms such as nasal obstruction, nasal discharge, sense of smell and a reduction in TNF-α, calprotectin and human β-defensin 2 concentrations.