Supplemental Efficacy in Tuberculosis Patients: A Systematic Review

ABSTRACT


Introduction
Tuberculosis cases were recorded in Southeast Asia (43%), Africa (25%), and the West Pacific (18%) in 2020.Out of the 30 countries that contribute the most to tuberculosis worldwide, eight countries account for two-thirds of the total, with India accounting for 26%, China 8.5%, Indonesia 8.4%, the Philippines 6.0%, Pakistan 5.8%, Nigeria 4.6%, Bangladesh 3.6%, and South Africa 3.3% [4].A significant close relationship was discovered between nutritional deficiencies and the incidence of tuberculosis.Patients with tuberculosis often have poor nutritional status [8].
Several previous literature reviews have indicated that neuropathy prevention in tuberculosis patients can be achieved through the administration of additional micronutrients, such as vitamin B6 [17].In addition, previous studies utilizing systematic reviews and meta-analyses to evaluate the efficacy and safety of vitamin D supplements in tuberculosis patients concluded that vitamin D had no impact on the improvement of tuberculosis patients [26].Although several additional supplements for clinical improvement in tuberculosis patients have been studied by previous researchers, only specific micronutrient and macronutrient supplements like vitamin D and vitamin B6 have been discussed [7,16,19).While many previous studies have examined the effectiveness of various types of supplements.For example, the addition of Channa striata extract supplements, which are snakehead fish extracts, supplementation of a type of probiotic containing the Lactobacillus casei strain known in Yakult packaged beverages, and additional supplementation of herbal plants for clinical improvement in tuberculosis patients [13,14,21].Therefore, the purpose of this study was to update the existing evidence of supplementation's clinical efficacy for tuberculosis patients.

Materials and Method
The research was conducted utilizing a systematic literature review approach, with data collected systematically by identifying, evaluating, and interpreting all findings to answer research questions (Table 1).Modeling a clinical question form known as PICO/PIOT, which is used to answer research questions, is the first step in the research process.P=patient/population/problem, I=intervention/prognostic factor/Issue, C=comparison/intervention, and O=outcome/result.Following the PIOT method, a research question was developed to carry out this systematic review: is there any clinical improvement in patients with tuberculosis who are given additional supplementation?

Database keyword search phases
The keywords "tuberculosis and vitamin treatment" and "tuberculosis and nutrition" were used to search three databases (Pubmed, Direct research, and Sage) for publications published between 2018 and 2022 with the keywords "tuberculosis and vitamin treatment" and "tuberculosis and nutrition."Articles that could be accessed, additional intervention research, research designs using RCTs, case-control, cohort, and experimental studies, and study subjects who had been diagnosed with tuberculosis were used as criteria for inclusion.Articles that use a literature review, case report, cross-sectional, or descriptive research method are not allowed.Database keyword search procedures are shown in Figure 1.The original search yielded 14,249 articles, which were reduced by 1 to 14,248 articles.The remaining 3,503 articles and 24 publications that met the research design criteria were omitted because they could not be obtained.Studies that met the following inclusion criteria were included: they were published in English, were available in full text, were submitted via digital media platforms, and had sufficient data; then, we found as many as 10,745 articles.Seventeen studies were removed because the study participants did not have tuberculosis, and there was no extra supplemental medication; the remaining seven articles were included in this analysis (Figure 2).

Results
The subjects in the seven articles were tuberculosis patients undergoing anti-tuberculosis treatment (control group), and patients undergoing anti-tuberculosis treatment and supplementation (case group) (Table 2).Males and females varied from 6 to 65 years of age.Four articles incorporate Body Mass Index characteristics (BMI), one article made use of the nutritional status measurement and 1 other article did not include body mass index characteristics [2,6,13,14,23,25].Three articles measured serum vitamin levels [2,23,27].While four other articles did not [2,6,13,14].Blood tests, chest X-rays, sputum culture, lung function, vitamin levels, and tuberculosis symptom scoring were performed on subjects before and after the study, as shown in Table 3.There are only three articles that report on the findings of research on supplement side effects (Table 4
According to the prevalence of tuberculosis patients who suffer more vitamin D deficit than the group without tuberculosis, vitamin D deficiency is linked to the incidence of tuberculosis [24].Furthermore, vitamin D deficiency in tuberculosis patients results in higher levels of sputum smears       as well as more extensive lung lesions, indicating the severity of the disease [11].Vitamin D is a fatsoluble vitamin that can be obtained from the sun or foods such as egg yolks, liver, butter, and fish oil.Vitamin D is absorbed by the skin (from sunshine), processed in the liver, and excreted in the kidneys before it can be carried in the blood and released to have its full effect on the body [3].Vitamin D receptors, CYP27B1 enzymes, and CYP24A1 enzymes are required for vitamin D metabolism, which is influenced by inflammatory mediators in immune cells and epithelial cells.Serum 25 (OH) 2 D levels in the body can be influenced, particularly by cigarette smoke and the inflammatory cytokines TNF-α, IL-1β, IL-17A, and TGFβ1 [20].Activating macrophages and monocytes, and regulating the development of antigen-presenting cells and natural killer which are used to combat viruses and bacteria, are just a few of the functions of vitamin D in the body in addition to maintaining bone health.[5].
Lactobacillus casei is a type of good bacteria that can be found in a variety of foods.Lactobacillus casei has the ability to control the expression of cytokines such as interleukin-6, interleukin-12, and interferon-g [15].According to a prior study, Lactobacillus casei increases the activity of macrophages, which lowers the risk of infection [18].Lactobacillus casei has been shown to prevent elderly weight loss by producing organic acids in the digestive system that convert fiber into energy-producing substances [10].A database search on the effects of probiotics revealed that they could provide health benefits such as lowering the risk of heart disease, acting as an anticarcinogen, and lowering the risk of sepsis and lung infections, making probiotics a therapeutic option in the future [30].Furthermore, previous research using prebiotic and antibiotic-treated rats found that they reduced interleukin-1α serum levels compared to the control group and also protected the balance of digestive tract microorganisms after antibiotic therapy [31].
Snakehead fish called Channa striata, which inhabits fresh water, has 70% protein [12].This fish has a lot of protein, which helps wounds heal, and has anti-inflammatory and fever-reducing effects.(Snakehead Fish (Channa striata) and Its Biochemical Properties for Therapeutics and Health Benefits, 2018).Baihe gujin is a traditional Chinese medicine that is used to cure lung problems.It is composed of many herbal plants, including Lilii bulbus, Ophiopogonis radix, Rehmannio viride radix, Rehmannia praep radix, Paeonia alba radix, Fritillariae cirrhosae bulbus, Platycodi radix, Scrophulariae.It has been demonstrated that Ophiopogonis radix is widely utilized in conjunction with contemporary therapy to cure tuberculosis [29].Numerous ingredients found in conventional medicines have been found to have biological effects on the body, such as anti-inflammatory and anti-cancer capabilities [28].In pulmonary fibrosis research on rats, Lilii bulbus was discovered to have an anti-inflammatory and pro-macrophage impact [1].
Ferulic sodium is one of the parts of this herb.Previous research findings on mice have shown that ferulic acid has an anti-inflammatory effect and speeds up the healing process [32].One of the components of this herb, angelica sinensis clam root, stimulated the immune system's helper T cells and promoted macrophages' production of IL-2, IL-4, IL-6, and interferon-y [9].
Several weaknesses were acknowledged in this study: first, small doses of vitamins did not affect patients; second, the treatment group received a mixture of vitamins; third, the number of samples was insufficient; and fourth, numerous articles failed to mention any negative effects.However, some of the strengths of this article are as follows: first, the supplements in the article are more diverse; second, the supplements or additional nutrients that are used can be easily obtained, such as good fish (Channa striata extract) and Lactobacillus casei found in Yakult packaged drinks; and third, the age characteristics of the population in the article are more diverse, so that additional supplementation can be used by more than one age group.Therefore, we argue that this article's findings can be applied to tuberculosis patients.

Conclusion
According to the results of this comprehensive review study, adding supplements to the regimens of patients with tuberculosis provided variable degrees of clinical benefit.The dosage and kind of supplement used will determine how well it works when added.It is envisaged that numerous researchers will carry out studies on supplemental or supplementary nourishment for tuberculosis patients, particularly dietary supplements or herbal plants that are simple to obtain.

Figure 1 .
Figure 1.Database Keyword Search Procedures

Table 1 .
Research Questions Using PIOT/PICO

Table 3 .
Evaluation of Success Criteria for Adding Supplements