In this study, we evaluated the serum zinc level in 52 elderly patients living in a nursing home. Previous research has shown that the serum zinc level in the general population decreases with age, as a result, many elderly subjects have a zinc deficiency. There are many possible explications for the observed decrease in zinc levels. First, zinc intake from foods decreases with age and second, the elementary absorption of zinc from the intestinal tract decreases with age. The third possibility is that, in those taking many medications, zinc is chelated by the drugs [12]. Drugs with a chelating function bind to circulating zinc and are excreted in the urine; thus, it is less readily absorbed [13, 14]. Aside from chelating agents, drugs that increase the pH level in the gastroenteric tract, such as proton pump inhibitors, may also decrease zinc absorption[15].
As in many previous reports, there was a positive correlation between serum zinc and albumin levels in the enrolled subjects. This was expected, because zinc is known to mostly bind to albumin in the blood [16]. Meanwhile, in this study, the serum albumin concentration was not affected by zinc supplementation. In addition, there was no significant correlation between the serum albumin level and the time in S-SPT, suggesting that the improvement in swallowing function depended solely on the improved zinc concentration, not on the serum albumin level or nutrition level. Generally speaking, zinc is involved in protein synthesis and enzyme activation; thus, after an adequate supplementation period, zinc supplementation may eventually increase serum albumin level, BMI, and body weight. However, in this study, we could not confirm such changes in nutrition level-related markers after zinc supplementation, possibly because of the relatively short supplementation period of only two to three months. Future research should focus on the long-term effects of zinc supplementation in elderlies with zinc deficiency.
The serum zinc level in one patient, who did not take proton-pump inhibitor and other chelating agents, was not improved after zinc supplementation. The patient had a long history of having a bedridden status; although the reason is unclear, intestinal zinc absorption may have been compromised due to the already deteriorated health condition.
To explain the observed correlation between serum zinc levels and swallowing function, we hypothesized that zinc supplementation may have promoted functional improvement of swallowing-related neurons and increased the number of taste buds in the pharynx and larynx, leading to improved function of sensory input in the swallowing reflex pathway. In contrast to the taste buds in the tongue which exclusively function as gustatory receptors, those in pharyngeal and laryngeal regions are believed to also prevent pulmonary aspiration[12]. Additionally, several previous articles have reported that intracellular carbonic anhydrase activity is involved in the relationship between taste receptivity and zinc in the tongue[13, 14]. It is also suggested that carbonic anhydrase may have some roles in the function of cells with these receptors and as well as neural transmission in the larynx.
Capsaicin is a molecule that is known to be associated with S-SPT anßd is believed to be useful in preventing aspiration pneumonia in the elderly[17]. Increased serum zinc level is suggested to increase capsaicin levels as well, thereby improving swallowing function. In this study, we did not check the levels of capsaicin; the further evaluation would be important to be able to clinically elucidate the correlation between zinc and capsaicin.
Zinc play an important role in respiratory tract infection including bacterial and viral infection [18]. Zinc is considered as a potential supportive therapy in the treatment of Coronavirus Disease 2019 (COVID-19) infections due to its indirect antiviral as well as direct immunomodulatory effects [19]. Zn2 + cations, especially in combination with Zn ionophore pyrithione, were reported to inhibit the activity of SARS-coronavirus RNA polymerase (RNA-dependent RNA polymerase, RdRp) by decreasing its replication [20]. COVID-19, like SARS-CoV, requires angiotensin-converting enzyme 2 (ACE2) to enter target cells (Hoffmann et al. 2020),and Speth et al. demonstrated that zinc exposure (100 µM) could reduce recombinant human ACE-2 activity in rat lungs[21]. Since direct data in the human on anti-COVID-19 effects of zinc are lacking, It would be interesting to observe not only swallowing function but also the correlation between Zn supplementation and COVID-19 infection to cope with this pandemic disease.
Cerebrovascular diseases are among the most common causes of dysphagia; damage in different areas within the central nervous system could promote dysphagia, such as delayed swallowing reflex, inadequate swallowing motion, and abnormal swallowing pattern. Impairment in swallowing reflex is not an only a consequence of dysphagia, and other multiple factors are often involved [22]. In this study, some of patients had brain vascular disease. In most of these patients, serum zinc levels were not improved after oral zinc supplementation, and the swallowing function was only minimally affected. Meanwhile, those whose serum zinc levels were severely decreased without the history of cerebrovascular diseases responded well to the oral zinc supplementation both in their serum zinc level and in their swallowing functions. Future research in the elderly with zinc deficiencies should better stratify their treatment population to more clearly identify factors that distinguish responders and non-responders to oral zinc supplementation.