morbidity in children receiving zinc alone compared with those receiving placebo, and this difference was statistically significant for the proportion of days with cough (p<0.05). In contrast, children in the Zn + vitamin supplement group had significantly higher morbidity rates than the Zn group for the incidence of severe diarrhea, cough, and fever (all p<0.05). Adding baseline iron status (serum ferritin <12 μg/L) to the model, as an interaction factor with treatment group, did not explain the difference in morbidity between groups. A study of zinc and micronutrient supplementation in children in South Africa also found no significant benefit of the interventions in reducing the incidence of diarrhea and respiratory infections [199]. However, morbidity was not the primary outcome in many of these studies, and lack of power due to small sample sizes is a major limitation.
In our study, after 6 months of using the multi-VCDD supplement and warm Galangal leaf powder, the IgG concentration of the intervention group was significantly improved compared to the control group. Increased IgG enhances the ability to activate complement to help the body fight against exogenous antigens (viruses, bacteria and toxins). IgG plays a particularly important role in the secondary response of the immune system. When the immune system is exposed to an antigen for the first time, the primary response is performed by IgM and is immediately followed by an increase in IgG concentration. IgG remembers the antigen, so the next time it is exposed to the antigen, the immune system will respond immediately with specific IgG. Therefore, high IgG concentrations in the serum help children have fewer respiratory diseases than the group of children who did not receive intervention. The immune system, in which IgG is improved thanks to the supplementation of VCDDs such as vitamins A, C, iron, zinc... has been shown by many studies. Recently, some scientists have studied and evaluated the effectiveness of using natural medicines derived from plants containing many polyphenols to protect the digestive and respiratory mucosa from attacks by some viruses and pathogenic bacteria.
The effect of polyphenols on improving respiratory infections in children may be due to their antibacterial properties. Cristina Esposito et al (2021) [210] conducted a randomized, double-blind, placebo-controlled clinical trial of a polyphenol mixture from propolis for the treatment of respiratory infections.
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Limitations of the Study and Future Research Directions
upper respiratory tract. This study was conducted on 122 healthy adults with a history of mild upper respiratory tract infection. Participants, randomly assigned to receive either propolis spray or placebo, underwent four outpatient visits. The total polyphenol content of the propolis spray was 15 mg/ml. The dosage was 2-4 sprays three times/day (corresponding to 12-24 mg polyphenols/day), for five days. The duration of the study was 8 weeks. After 3 days of treatment, 83% of subjects treated with propolis spray had symptom relief, while 72% of subjects in the placebo group had at least one residual symptom. After five days, all subjects had resolved all symptoms. This means that the resolution of symptoms of uncomplicated mild upper respiratory tract infection occurred two days sooner, instead of the five days recorded in the control group. There was no association between oral administration of propolis spray or placebo and adverse events. Polyphenolic compounds extracted from Galangal have also been shown to have similar anti-microbial properties in the urinary and gastrointestinal tracts. Aroonlug Lulitanond et al. (2019) published a study on the extraction of bioactive compounds from Galangal with anti-microbial properties [135]. The flavonoids found in this study were myricetin, quercetin, rutin, and kaempferol, respectively. In addition, the most common phenolic compounds were the hydroxybenzoic acid group (including gallic acid, syringic acid, protocatechuic acid, and p-hydroxybenzoic acid) and the hydroxycinnamic acid group (ferulic acid). These compounds in Apinia zerumbet extract have some potential antibacterial activity. The data showed that Alpinia zerumbet extract could inhibit both Gram-positive reference bacteria and six Gram-negative bacteria at different concentrations. S. aureus ATCC 29213 was the most sensitive strain to Alpinia zerumbet extract. These evidences confirm that Alpinia zerumbet rhizome extract has antibacterial activity and may have potential for developing products for the treatment of infections. Cristiane P.Victório et al. also conducted the distillation of essential oil from Alpinia zerumbet leaves [201]. The leaf oil of A. zerumbet had inhibitory effects on Escherichia coli (Gram-), Staphylococcus aureus MRSA (Gram+) and Staphylococcus epidermidis (Gram+), and

Cryptococcus neoformans T444 and Candida albicans.
Other studies have suggested that polyphenols have immunomodulatory and anti-inflammatory roles, including protection of the respiratory epithelial cell barrier, regulation of alveolar-derived macrophages and monocytes, neutrophils, T lymphocytes, as well as their cellular functions, such as the production of inflammatory mediators (cytokines, chemokines, and soluble BN receptors) and the activation of inflammasomes. Therefore, since the beginning of the COVID-19 pandemic, many scientists have proposed and recommended the potential use of polyphenols as pharmacological agents to enhance immunity against SARS-CoV-2 infection and counteract the severe “cytokine storm” during the pandemic [202].
The use of natural medicines in rural or developing populations is often attributed to the lack of access to modern medicines for common infectious diseases and traditional beliefs in the natural, beneficial properties of plants and plant-derived products and the high polyphenol content of fermented Galangal leaves in the products. Therefore, during the 6-month intervention period, the concentration of IgG humoral immunity increased and the number of days with respiratory infections and the number of days with each episode of diarrhea and respiratory infections in children was reduced.
Although there have been some studies on the intervention of multivitamin supplements or polyphenols extracted from plants on the status of infection, the clinical trials on subjects with different infection status, small scale and inconsistent results. In addition, to see the pharmacological effects of highly bioactive compounds from plants also depend on the dose and time. Therefore, more studies on supplementing polyphenols from Galangal as well as combining multivitamin supplements with polyphenol compounds from Galangal on many different subjects are needed to collect accurate, scientific information on the mechanism of action and intervention effectiveness on stature, physical strength as well as on the disease status of children.
4.4. Some limitations in the research implementation process
- The study was conducted for 6 months at a kindergarten. Due to professional conditions, kindergarten teachers could not assess the status of upper respiratory tract infection and lower respiratory tract infection, acute infection and chronic infection. These factors may affect the effectiveness of changing the concentration of Hemoglobin, IgG, IgM of children during the intervention period.
- Our study only evaluated the effectiveness within 6 months, so we have not seen the effectiveness of disease prevention and treatment for SDD, anemia and diarrhea. Longer-term research is needed to clearly see the role of multivitamins and polyphenols in warm Galangal leaf powder in the treatment of nutritional diseases and digestive infections.
- In this study, we did not have the conditions to evaluate the individual effects of multivitamins and Galangal leaf powder on the nutritional status, immune index and infection status of children. Separate studies are needed to evaluate and explain the mechanism of influence of each factor on the physical development and health status of children.
CONCLUDE
The results of the study on the effectiveness of multivitamin supplementation and warm Galangal leaf powder in improving nutritional and immune status in 36-59 month old Thai ethnic children in Son La city gave the following conclusions:
1. Nutritional status of 2,471 children aged 36-59 months at 9 kindergartens, Son La city:
- The average weight and height of boys were 14.12 ± 1.95 kg and 95.86 ± 4.74 cm, and of girls were 13.62 ± 1.72 kg and 95.03 ± 4.68 cm.
- The mean Z-scores of children were all less than 0: mean WAZ was -1.12 ± 0.87, mean HAZ was -1.57 ± 0.85, mean WHZ was -0.31 ± 1.13.
- The malnutrition status of children aged 36-59 months in Son La city is as follows: stunting 31.0%, underweight 13.3%, wasted 5.4%, overweight and obesity 3.2%. The total number of children with one or a combination of malnutrition is 38.6%.
- Stunting among children aged 36-59 months in Son La city is still very high compared to the threshold for classifying the level of malnutrition in the community. Thai ethnic children have the highest rate of stunting among the three ethnic groups (33.6%). Children in suburban areas have a higher rate of stunting than children in the city center.
2. The effectiveness of supplementing multi-micronutrients and warm Galangal leaf powder on the nutritional status of 36-59 month old Thai ethnic children has the following results:
- Supplementing multi-micronutrients and warm Galangal leaf powder has had a positive effect on improving the nutritional status of 36-59 month old Thai children. After 6 months of intervention, the difference in weight, height, WAZ, HAZ index, and Hemoglobin concentration of the intervention group compared to the control group was 0.4 kg, 0.7 cm, 0.27 WAZ and 0.34 HAZ, respectively.
- Intervention has no effect on disease prevention, treatment of malnutrition and anemia in children.
children study
3. The effectiveness of supplementing multi-micronutrients and warm Galangal leaf powder on the immune index IgG, IgM and infection (diarrhea and respiratory infection) of 36-59 month old Thai ethnic children in Son La city shows that:
- After adjusting for factors affecting the study's effectiveness, the intervention group had a higher IgG concentration than the control group by 19 mg/dL (p<0.05), the difference in IgM concentration was not significant (p>0.05).
- Supplementation of multi-micronutrients and warm Galangal leaf powder for 6 months reduced the average number of days of respiratory infection in each episode, and the total number of days of respiratory infection in the intervention group compared to the control group. The intervention did not have any effect on improving diarrhea in the children studied.
RECOMMENDATION
1. Based on the results of the study on growth, hemoglobin concentration and immunity of children under 5 years old, it is necessary to increase the use of multi-micronutrient supplements and warm Galangal leaf powder for children, especially for ethnic minority children in difficult areas with high rates of malnutrition and infection.
2. Continue to conduct research to evaluate the effectiveness of multi-micronutrient products combined with Galangal leaf powder on a larger scale, over a longer period of time in different groups of subjects to have solid scientific evidence of the effectiveness of the product.
LIST OF PUBLISHED WORKS
1. Khuc Thi Hien , Nguyen Huu Chinh, Bui Van Tuoc, Ha Anh Duc, Nguyen Van Le, Bui Thi N hung, Nutritional status of children aged 36-59 months at some kindergartens in Son La city in 2015 , Nutrition and Food Journal, No. 17 (4) - 2021.
2. Khuc Thi Hien , Nguyen Do Van Anh, Nguyen Thi Huyen Trang, Ha Anh Duc, Nguyen Van Le, Bui Thi N hung, The effectiveness of multi-micronutrient supplementation and Shell ginger leaf powder in improving nutritional status and immune index of Thai ethnic children 36-59 months old in Son La city , Journal of Nutrition and Food, No. 17 (4) - 2021.





