Currently, there is a wide discussion about the effects of the pH of drinking water and its consequences on human health, such as its relationship with inflammation and cancer (25). However, there is little scientific evidence supporting this association.
In the present study, we found a significant increase in the expression of 2 microRNAs, miR-29c and miR-135b, after the consumption of alkaline water for 5 consecutive months, as well as an improvement in gastritis as evaluated by a second EGD; i.e., 42% of the patients who had moderate gastritis in the first EGD had mild gastritis in the second EGD, according to the Sydney classification system. It is also worth noting that the patients did not undergo pharmacological treatment for gastritis during the intervention period and were not instructed to change their diet during the period.
Gastritis is considered a preneoplastic condition, as it participates in gastric carcinogenesis in the early stages of the process, followed by gastric atrophy, ulcerations, intestinal metaplasia, dysplasia and, finally, malignant neoplasia (4, 26, 27). Thus, the improvement in gastritis observed in the present study with the use of alkaline water may represent a protective factor of inflammation in the gastric mucosa. Thus, this simple lifestyle change may act positively in the early stages of the carcinogenesis cascade of GC.
Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in the world; however, although they are generally considered safe, they have several adverse effects associated with prolonged use (28, 29). These medications are associated with an increased risk of the development of premalignant lesions (fundic gland polyps, worsening of gastric atrophy and metaplasia) and GC, particularly in individuals infected with H. pylori, especially when PPIs are used for over one year (28–30). The use of alkaline water does not compare with the mechanism of action of PPIs because there is no inhibition of acid secretion but, rather, a reduction in exposure to acidic substances of a mucosa that is damaged by gastritis (reference).
miR-29c is commonly described as a tumor suppressor because it inhibits the proliferation, invasion and migration of malignant cells. Decreased expression of this microRNA has been reported in several human malignancies, such as pancreatic cancer (31), breast cancer (32), prostate cancer (33), hepatocellular cancer (34), nasopharyngeal cancer (35) and GC (10, 36).
The miR-29c expression levels were significantly decreased (p < 0.001) in GC tissues compared to normal tissue (37). In addition, it has been demonstrated by in vitro and in vivo assays that the increased expression of this miRNA suppressed tumor growth through the downregulation of ITGB1 (β1 integrin, also known as CD29) (37).
As previously described, miR-29c expression levels gradually decrease as gastric carcinogenesis progresses at different stages of mucosal aggression, demonstrating a direct correlation between the loss of mir-29c expression and the tumorigenesis of this cancer (10). Thus, in our study, the increased expression of this miRNA after the consumption of alkaline water may suggest that its frequent use may function as a modifying factor of the epigenetic environment of these tissues, providing an environment with lower chances of carcinogenic progression. Transfection of the miR-7 precursor into AZ521 and Kato III GC cells significantly inhibited cell proliferation capacity (13).
miR-135b has been described in the literature as an oncomiR in most tumor tissues, such as colon cancer (38), lung cancer (39), oral cancer (40) and breast cancer(41), but few studies have evaluated its role in gastric tissue. Vidal, Cruz (10) observed that miR-135b expression was increased in gastric lesions when compared with normal gastric mucosa but was decreased when gastritis tissue was compared with cancer tissue; thus, its role in the various stages of gastric carcinogenesis remains uncertain.
miR-135b has been described as a tumor suppressor in osteosarcoma, and the MYC gene, which is related to the progression of several tumors, is its direct target (42). That role is similar to that observed for prostate cancer, for which Wang, Tao (43) observed a decrease in miR-135b expression in prostate cancer tissues compared to normal tissues, acting as a tumor suppressor by inactivating the STAT6 pathway, known as oncogenic in several tumors. Thus, as the signaling pathways and activity of this miRNA are not yet certain, we cannot affirm or suggest protective or deleterious effects generated by increased miR-135b expression after alkaline water consumption.