The results of the present study show that although serum zinc level of recurrent herpes labialis patients was lower than healthy individuals, but this comparison was not significant. What is interesting is that the duration of lesions was significantly higher in patients with low serum zinc levels. And also the recurrence rate in the past year was lower in patients with higher zinc levels.
Why this element may have an effect on reducing the recovery time of this lesion or reducing the recurrence of herpes disease may be due to its various effects in the human body. Zinc is an essential element for the natural function of cells, tissues and organs of the body. As a factor, it leads to the enhancement and migration of keratinocytes during wound healing. Moreover, Zinc has many roles in metabolism. Zinc is involved in the metabolism of nucleic acids and proteins and in the processes of cell differentiation and proliferation. Zinc ions stimulate lymphocyte DNA synthesis in a few days, and about 10–40% of lymphocytes become lymphoblast. Additionally, unsaturated zinc-8 hydroxiquinoline complexes in animals stimulate lymphocyte synthesis.(18, 19)
Moreover, in relation to host immunity, Zinc has the capacity to safely control viruses by stimulating cellular immunity. T-Lymphocyte response is a cellular immune based immunity (CMI). CMI is important in protecting against viral, fungal and protozoic infections, as well as against malignant and autoimmune diseases. Zinc appears to increase the number of effector and helper T-cells, either the precursors of the antibody-forming cells or the increased activity of suppressive cells.(9, 13, 20) In a study conducted by Barman et al., Zinc deficiency has been shown to reduce host immunity by reducing circulating T cells and decreasing the phagocyte activity of other cells, which generally affects cell-mediated immunity.(21)
Although zinc deficiency may have many effects, but clinical evaluation of this deficiency is not easy, because the signs and symptoms are non-specific. Signs associated with zinc deficiency include: decreased plasma zinc levels (< 70 µg / dL), decreased serum alkaline phosphatase, retinal alcohol in the retina (leading to night blindness) and decreased plasma testosterone levels, T- lymphocyte dysfunction, decreased collagen synthesis (resulting in poor wound healing), and decreased RNA polymerase activity in different tissues. (8, 17)
Recently, the role of zinc compounds in the prevention and control of many diseases and abnormalities of humans and animals has been considered. The use of zinc compounds in order to strengthen the local defense system, reduce the inflammation of the bacteria and produce epithelial cells and endothelium vessels in the repair of foot injuries has been proven. Many studies indicate that administration of systemic or topical zinc helps reduce the recovery rate of RHL.(10–12, 14, 19)
In a study conducted by Khozeimeh et al., in 2012, salivary zinc was compared between people with recurrent herpes labialis in both conditions of disease and recovery (21 days after the improvement of lesions of Herpes) and healthy people. The result showed that zinc level was significantly different, in disease state compared to recovery stage and recovery compared to healthy subjects. In this study, there was no significant correlation between zinc levels and age of patients, sex, recurrence rate and duration of healing.(16) However, in our study, serum zinc levels in subjects with the history of herpetic lesions were less than healthy individuals, but this difference was not significant. One of the reasons for this difference is that saliva is probably not an exact criterion for measuring the amount of zinc in the body. As it is shown in a study conducted by Freeland-Graves and colleagues, comparing whole saliva and salivary sediment after the administration of a low zinc diet (3.2 mg / day)in 12 women for 22 days. The zinc level of saliva and salivary sediment (centrifuged saliva) were measured before and after the start of the study. The results were that zinc saliva levels remained constant throughout the study, while zinc levels in salivary sediment significantly increased 22 days after the adminstration. As a result, complete saliva is by no means an acceptable benchmark for the evaluation of zinc intake.(22)
It is noteworthy that in several studies it has been determined that serum zinc is the most widely used biomarker for assessing the status of zinc in the population. Serum zinc concentration indicates recent consumption of zinc or regular zinc intake, which means that in populations with low zinc diet, the serum zinc level is lower, indicating high zinc deficiency risk. These studies showed that the best time to measure serum zinc was whilst fasting in morning.(17, 23)
In another article, published by Femiano et al. in 2005, they examined the effect of zinc on RHL. In this paper, 20 patients (including 12 women and 8 men) with an average age of 26.6 with a history of RHL more than 6 times per year and a recovery period of more than 8–14 days were treated with zinc sulfate 22.5 mg twice daily for 4 months. Patients were followed for 12 months. The study concluded that herpes ulcers decreased by less than 4 times a year and the recovery period were reduced to less than 7 days at each relapse. As a result, this study showed that systemic zinc sulfate reduced the relapse rate and the period of RHL. This study also found that people with lower serum zinc had a longer recovery period, as well as a higher rate of relapse in a year. However, our study did not address the treatment of such individuals.(24)
In a study conducted by Brody et al. they used a zinc sulfate solution on the site of herpes lesions on the skin and the oral mucosa (used on the skin at a concentration of 0.05 − 0.025% and on the mucus at a concentration of 0.01–0.025%). This study also showed that treatment with this solution on the skin prevents post-herpetic erythema multiform in addition to its herpes preventive role.(25)
In a laboratory study conducted by Max Arens et al., they investigated the effects of different concentrations of different zinc salts (zinc acetate, zinc lactate, zinc sulfate, zinc gluconate) on isolated HSV virus in culture medium. The results showed that isolated HSV, in laboratory conditions, is effectively inactivated by treatment with Zinc salts, and the degree of inactivation of the virus depends on the type of HSV, zinc concentration and treatment length.(26)
In a study published by Antoine and colleagues in 2016, ZOTEN (zinc oxide tetrapod nanoparticle) was used as an intravaginal vaccine in female rats. The ability to inhibit HSV-2 by ZOTEN reduced clinical symptoms and decreased rat death. ZOTEN inhibited recurrent infection with increasing T cell-mediated and antibody-mediated response. Overall, the effect of the vaginal microbial vaccine against primary and secondary vaginal herpes virus infection was determined. (27)
In the case of other viral disease and body minerals, in a study conducted by Okwara et al. 51 adult patients with HIV viral infection and 48 healthy people were selected. Selenium, zinc and magnesium were measured. All the minerals were lower in HIV-infected individuals compared to healthy subjects. The difference in the type of viral disease and the difference in sample size may be due to the differences in the results of the current study with this study.(28)
It is worthy to note that due to the fact that herpes is a common and self-limiting disease, usually referral to a dermatologist or dentist is rare, therefore patient selection was somehow difficult. Also encouraging the patients for blood sampling was not easy. Further studies with larger sample sizes are suggested. It is also suggested that other viral diseases, should be checked in regard to zinc level. It is reasonable to compare saliva and serum simultaneously. Moreover comparison of plasma zinc levels both disease and recovery state can be beneficial.