3.4. Phytotherapy
Out of the given number of interviewed people, approximately one quarter, 23.24% (total of 396 persons) declared themselves as users of phytotherapy with the purpose of prevention or treatment of COVID-19. Bearing in mind relatively high percentage of phytotherapy users reported in the present study, this may suggest that medicinal plants were mainly used in prevention of COVID-19. In previously reported studies, it was found that phytotherapy was the most frequent form of therapy (beside the conventional drugs), closely followed by the use of nutritional supplements and vitamins [
24,
26]. Other results contrast this, reporting vitamin supplements as the most frequent type of therapy [
21,
22].
A statistical testing comparing differences between phytotherapy users and non-users showed differences in some of the compared variables, namely age, level and type of education, employment status, monthly income, region of residency and marital status. Additionally, it was shown that there are differences between users and non-users of phytotherapy, regarding the use of conventional drugs and non-herbal dietary supplements. The detailed results are presented in
Table 4.
The list of the most frequently used medicinal plants is given in
Table 5.
Since the break-out of the pandemic, numerous medicinal plants were investigated and evaluated for their potential in the prevention and treatment of COVID-19 [
27]. Among the reported medicinal plants (
Table 3), the most frequently reported was garlic (
Allium sativum L., Alliaceae). The positive effects of garlic use against COVID-19 are presumed result of immune activation, mediated by the stimulation of macrophages, lymphocytes, and natural killer cells. Additionally, it was observed that garlic can modulate cytokine secretion and synthesis of immunoglobulins [
28]. Garlic was also frequently reported in other studies investigating the use of phytotherapy in COVID-19 [
19,
25,
29]. The second most frequently used plant in this research was ginger,
Zingiber officinale Roscoe, Zingiberaceae. This plant was previously tested in COVID-19 patients, in combination with Echinacea, where it was found that the application reduces coughing, muscular pain, and shortness of breath [
30]. The third most frequently used plant was chamomile,
Matricaria recutita L., Asteraceae. Although not clinically tested in COVID-19 patients, this plant has numerous confirmed biological and pharmacological activities (with anti-inflammatory being main one), potentially useful against this disease [
31]. In vitro studies investigating potential of
Mentha species against coronavirus demonstrated that essential oil of these species can inhibit the replication of virus in the infected cells [
32].
Investigating the number of used medicinal plants, it was found that the respondents were using approximately six plants on average (mean 5.95, median 5). Furthermore, the application of association rules technique on dataset describing the medicinal plants used by respondents for the treatment or prevention of COVID-19 showed that the most commonly combined were chamomile and mint, garlic and ginger, garlic and cinnamon (
Supplement S2a). Bearing in mind the previously mentioned potential of each plant, it can be assumed that plant combinations can counteract more than one step of viral infection. Combination of mint and chamomile potentially inhibits the viral replication and reduces the subsequent inflammation, while combination of garlic and ginger stimulates immune system and reduces the negative effects of coronavirus in respiratory system.
Phytotherapy users listed different reasons for its application during the COVID-19 pandemic. Most of them reported a positive effect on the immune system (367 RU). The second most frequently reported reason was a positive effect on the respiratory system (135 RU), followed by a presumed effect in the prevention and treatment of coughing (94 RU). Other reasons for phytotherapy use included: a direct effect on the coronavirus (25 RU), an antipyretic effect (19 RU), etc. In similar studies investigating the reasons for phytotherapy application, some of the main reasons for phytotherapy and other CAM uses were the prevention of coronavirus infection and the reduction of anxiety [
20]. Additionally, the improvement of general well-being, and nutritional supplementation due to an inadequate diet [
33] were also listed as reasons of use. However, the majority of other studies found a stimulative effect on the immune system as the main reason for the use of medicinal plants [
19,
22,
33], as it is the case in the present study as well.
The most frequent route of administration was peroral (394 RU). Inhalation was the second most frequent route, although with much less interviewees reporting it (60 RU), followed by the application on skin and mucosa (23 RU). Most frequently, medicinal plants were used in a form prepared by the users themselves (e.g., a tea beverage) (245 RU), which is consistent with the study conducted in Bangladesh [
26]. Moreover, plants were used in fresh or dried form, as part of a meal or salad (236 RU), or in a conventional form bought from pharmacies (91 RU). Moreover, interviewees used medicinal plants in a form prepared for them by someone else (e.g., essential oil, drops, tinctures etc.,) (60 RU). A study in Morocco, conducted among traditional herbalists, found that fresh herbs were most frequently used for the preparation of infusions [
34]. This can potentially be explained by the convenience of preparation, bearing in mind that infusion-type beverages are frequently consumed and readily accepted by users. A study conducted in Ghana, also reported the use of raw herbal material for the preparation of herbal medicines, although finished products were reported as more frequently used [
21].
Medicinal plants are frequently used. More than half of the people responded using them on a daily basis (54.11%). Besides that, 38.65% of phytotherapy users responded using plants two or more times in a week. The study in Ghana found that CAM users most frequently use the medicines on a daily basis, followed by weekly application [
21]. This is consistent with the results of the presented study, where the daily or weekly use of herbal drugs was the most frequently reported regimens.
The sources of phytotherapy information were various. Most frequent sources were populistic thematic literature (books and magazines) (162 RU), followed by the Internet (152 RU). Members of the family, partners, or close friends were also frequently pointed out as sources of information (151 RU). Some of the interviewees reported consulting medical professionals (doctor, pharmacist, dentist) (134 RU), while some reported consulting herb-collectors and employees of herbal material stores (29 RU). The results of other studies reporting on the main source of information are contrasting. In some studies, the Internet and social networks are often listed as the main sources of information on phytotherapy and other CAM [
20,
23,
24,
25]. Other studies report family and friends [
22,
25,
26], while some report health practitioners as sources of information [
21].
The attitudes concerning the efficacy and safety of phytotherapy against COVID-19 were also investigated. The results are presented in
Table 6.
Nearly half of the interviewees using phytotherapy considered it to be effective in the prevention of the COVID-19 disease; however, approximately one-third of people using phytotherapy responded, “I am not sure”. Other studies report similar results, with more than two-thirds of CAM users considering them to be effective in COVID-19 prevention [
21]. Regarding the effectiveness of treatment of an already present COVID-19 disease, phytotherapy was perceived as less effective than prevention. One previous study found that the majority (60.7%) of CAM users considered this type of therapy not effective against the disease [
24].
Considering the safety of phytotherapy, it was generally perceived as safe in the prevention of COVID-19, with approximately two-thirds of medicinal plant users declaring it safe. Similar answers were given regarding the safety of phytotherapy in treatment of an existing disease COVID-19. A study in Turkey found that respondents prefer CAM therapies precisely because of fewer side effects compared to conventional medicines [
24].
Approximately one-third of phytotherapy users (30.75%) stated they have informed their doctor about the use of medicinal plants. A third of users (35.25%) consulted a medical professional before the application of phytotherapy. A different study researching CAM use in the COVID-19 pandemic report a high percentage (55%) of respondents consulting physicians prior using dietary supplements; however, this percentage was significantly lower (23.2%) for the use of medicinal plants [
20]. A study in Bangladesh reported that patients prefer to seek the advice on herbal medicines from physicians rather than pharmacists [
26].
Some studies compared the use of dietary supplements (both herbal and non-herbal) before and during the declared pandemic of COVID-19, and it was found that the use of these supplements increased [
25]. Herbal practitioners in the United Kingdom also reported an increase in the number of patients interested in herbal therapy of COVID-19 [
35]. Finally, COVID-19 was not the only reason for herbal therapy—42.50% of persons using phytotherapy against COVID-19 were also using it in the prevention or treatment of other diseases and conditions.
3.5. Other Dietary Supplements and Specific Diets
Out of the total investigated number of people, a significant part (41.14%, 704) reported using non-herbal dietary supplements. The most frequently used supplements are listed in
Table 7.
Dietary supplements used by the respondents reported in this research (
Table 7) were also frequently reported by other research [
20,
22,
25,
26,
35].
Vitamin C, potentially the most frequently mentioned among vitamins, plays an important role in the human body, especially in the immune system. Interestingly, previously published studies report only its use in treatment of COVID-19, while the data on the prevention of the diseases are lacking. A universal conclusion cannot be made, although a beneficial effect is noticed in patients with various clinical presentations of the coronavirus infection [
36]. Zinc, as the second most frequently reported dietary supplement in this study, is an important microelement which inhibits viral entry and replication. Additionally, it was found in clinical studies that the use of zinc can reduce the incidence and duration of viral diseases [
37]. Concerning vitamin D, the popularity of this liposoluble vitamin has dramatically increased since the declared pandemic. Bearing in mind that the deficiency of vitamin D can increase the incidence or severity of viral diseases, supplementation with this vitamin could potentially reduce the risk of infection [
38]. The application of association rules technique on dataset describing the non-herbal dietary supplements used by respondents for the treatment or prevention of COVID-19 shows that the most commonly combined was vitamin C with zinc and vitamin D, (
Supplement S2b). Bearing in mind the previously mentioned mechanism of activity of given mineral and vitamins, it can be assumed that these two combinations can decrease the probability of coronavirus entry into the human organism, thus reducing the risk of infection.
Concerning the changes in specific nutrition regimens, only 7.16% (122) reported being on a specific diet with the purpose of prevention or treatment of COVID-19. Most frequently, people opted for a diet with increased amounts of fresh fruits and vegetables (100 RU), a diet with organic food (24 RU), followed by a vegetarian/vegan diet (21 RU) and raw food diet (11 RU).
It was found that a relatively small section of respondents (197, 11.56%) use both herbal and non-herbal dietary supplements. Using a previously described method (association rules technique), it was shown that in this sub-group of interviewees, garlic was most often combined with additional supplementation of vitamin C (
Supplement S2c). Although results were inconclusive for vitamin C, it can be suggested that both hydrosoluble vitamin and garlic display a positive effect toward cells of the immune system, thus acting against COVID-19 in an indirect mechanism.
Additionally, an even smaller portion of the respondents is using non-herbal dietary supplements in a combination with a specific diet for COVID-19 prevention/treatment—33, 1.94%.
Contrary to the results presented here, in the Iranian population it was found that people rarely use only one type of CAM, and more frequently several of them [
20]. Similarly, the use of more than one natural product was reported in the population of Saudi Arabia [
19] and Hong Kong [
22].
3.6. Multiple Correspondence Analysis
The application of a multiple correspondence analysis on variables describing the demographic characteristics of surveyed participants, as well as their habits and opinions regarding the application of medicinal plants, dietary supplements and special types of diet regarding the possible prevention/treatment of COVID-19, showed that the first two dimensions (Ds) describe around 17% of obtained dataset inertia. The computed coordinates of the recorded answers in the space defined by D1 and D2 (
Figure 1) show a grouping of participants of lower monthly income and lower level of education in the negative part of D1. They represent younger categories of evaluated participants, being younger than 35 years, mostly single and living in rural or suburban areas. These participants claim that they were not in contact with COVID-19 patients, do not suspect that they have or had COVID-19, nor were tested for COVID-19. Furthermore, they are mostly not using conventional medicines for treatment of some chronic conditions, but also did not apply medicinal plants, dietary supplements, or some special types of diet for the prevention/treatment of COVID-19. On the other hand, the positive part of D1 is reserved for participants aged more than 36 years, with higher monthly income and higher level of education (graduated from colleges or universities). They are mostly married (or divorced), or living in extramarital union, inhabiting urban areas. They are not sure whether they were in contact with a COVID-19 patient or if they currently have/have previously had COVID-19. A subgroup of these participants which was tested for COVID-19 got negative results. Furthermore, this group of participants applies conventional drugs for the treatment of some chronic clinical conditions, but was also using medicinal plants, dietary supplements, and special types of diet in order to prevent/treat COVID-19. Another special subgrouping of survey participants can be observed in the positive part of D1 and positive part of D2. These participants are older than 65 years, retired, were in contact with COVID-19 patients and were tested positive for SARS-CoV-2 infection, which represents a significant concern regarding the general sensitivity of this age to COVID-19.
These results are consistent with the results of previously published studies, where it was found that increase in age results in higher odds of using natural products or CAM [
19,
21]. Moreover, the use of conventional medicines increases the odds of phytotherapy use [
19]. Other studies found that female participants are more likely to use various CAM [
20,
21,
22]. A study conducted in Turkey, additionally stated that women who are married, with higher education, and higher monthly income are more likely to be users of CAM [
24]. Higher education is also pointed out as a predictor of use of CAM in a study conducted in Hong Kong [
22].
The application of a multiple correspondence analysis on the dataset describing the opinion of the medicinal plants users regarding their efficacy and safety of application, as well as their usage habits shows that the first two dimensions describe around 24% of recorded responses variability. The position of recorded answers in the space defined by the first two dimensions (
Figure 2) shows that the negative part of D1 is mostly reserved for participants recognizing medicinal plants as safe and effective in treatment and prevention of COVID-19. The level of their certainty regarding the stated subject varies from agreeing to completely agreeing, which basically separates this group in terms of D2. They are also using medicinal plants for other clinical conditions, whereas they tend to inform and consult with health professionals about the usage. On the other hand, the positive part of D1 is mostly reserved for the group of respondents being skeptical of the potential of medicinal plants application in the treatment or prevention of COVID-19, or totally denying it. They are also unsure regarding the safety of medicinal plants application, but interestingly, it seems that they apply medicinal plants more frequently (once a week; two or more times per week) than the group of respondents located in the negative part of D1. Unfortunately, this recorded higher frequency of usage is followed by total absence of reporting to healthcare professionals.
3.7. Strengths and Limitations of Present Study
To the best of our knowledge, this is the first study investigating the use of phytotherapy in the Republic of Serbia and the Republic of Srpska. This study had several limitations and advantages that should be listed. It was limited to literate persons, who understand the Serbian language, and additionally, bearing in mind that this survey was distributed via the Internet, and only people with web access were included. Moreover, as patients filled in the surveys by themselves, it is possible that some of them had memory bias. Although no formal validation of questionnaire was performed, a pilot survey was conducted; the feedback on the questions was evaluated, and necessary changes were made. This study was conducted before the appearance of vaccines in the Republic of Serbia and the Republic of Srpska, thus their impact on the use of phytotherapy and other CAMs was not possible to investigate. On the other hand, the study had several strengths. The survey successfully included a high number of interviewees from a relatively large geographical area of investigation. As it was presented in
Table 1, diverse socio-demographic groups were included, thus it was possible to obtain more data on the use of phytotherapy and other CAMs depending on these factors.
The data obtained in this study provide preliminary information on most commonly used herbal and non-herbal dietary supplements, their combinations, and the patterns of their use. This information is of importance in treatment of persons infected with coronavirus, as treating doctors and medical professionals should be aware of potential adverse effects and interactions of herbal and non-herbal therapy with conventional ones. For example, in this study, garlic was identified as the most frequently used medicinal herb. Bearing in mind the potential of garlic to interact with conventional drugs, doctors should be aware of the probability of patients taking this medicinal plant. Besides that, patients with milder form of COVID-19, could attribute this difference in clinical presentation precisely to use of medicinal plants and other CAMs. In the same example, further investigations are required to examine whether the intake of garlic results in shorter course of disease, less pronounced symptoms, etc., and which pattern of use brings most of benefits.