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Online Library: Tuberculosis (TB)

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting tuberculosis (TB). This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Vitamin D and tuberculosis.

Source: Nutrition reviews 2009;67(5):289-93

Author: Chocano-Bedoya P, Ronnenberg AG.

Affiliation: Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts,USA.

Abstract: Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status.

High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial.

Source: Lancet. 2011;377(9761):242-50

Author: Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, Packe GE, Moore-Gillon JC, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Woodward NJ, Venton TR, Barnes KE, Mullett CJ, Coussens AK, Rutterford CM, Mein CA, Davies GR, Wilkinson RJ, Nikolayevskyy V, Drobniewski FA, Eldridge SM, Griffiths CJ.

Affiliation: Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, UK.

Abstract: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. The authors undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2•5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36•0 days in the intervention group and 43•5 days in the placebo group. TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion, with enhanced response seen only in patients with the tt genotype. FokI genotype did not modify the effect of vitamin D supplementation. Mean serum 25-hydroxyvitamin D concentration at 56 days was 101•4 nmol/L in the intervention group and 22•8 nmol/L in the placebo group.Interpretation: Administration of four doses of 2•5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism.

Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

Source: Science Translational Medicine 2011 Oct 12;3(104):104ra102

Author: Fabri M, Stenger S, Shin DM, Yuk, JM, Liu PhT et al.

Affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, USA., Institute for Medical Microbiology and Hygiene, University Hospital of Ulm, Germany, Department of Microbiology, Chungnam National University School of Medicine, South Korea.

Abstract: Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. The authors report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.

Antioxidants

Total Antioxidant Levels Are Low During Active TB and Rise With Anti-Tuberculosis Therapy

Source: IUBMB Life 2004; 56(2): 101-106

Author: Wiid I., Seaman T., Hoal E.G., Benade A.J., Van Helden P.D.

Affiliation: MRC Centre for Molecular and Cellular Biology, Department of Medical Biochemistry, University of Stellenbosch Faculty of Health Sciences, Tygerberg, South Africa.

Abstract: In tuberculosis, oxidative stress is a result of tissue inflammation, poor dietary intake of micronutrients due to illness, free radical burst from activated macrophages, and anti-tuberculosis drugs. These free radicals may in turn contribute towards pulmonary inflammation if not neutralized by antioxidants. The aim of this study was to evaluate the total antioxidant status (TAS) of healthy and M. tuberculosis-infected persons from a high TB incidence community, as well as tuberculosis patients at various stages of antituberculosis drug treatment and to correlate results with plasma micronutrient levels. Blood plasma samples from TB infected patients and following antituberculosis drug treatment were assayed for TAS, vitamins A, E and zinc. Statistical analysis of results was by one-way ANOVA and the Tukey multiple comparison post test. Active TB patients showed a significantly lower TAS (P < 0.001) compared to the community controls. The results also show that TAS values increase during therapy. Results correlated with micronutrients vitamin A and zinc but vitamin E remained unaffected. The study suggests that total antioxidant status of TB patients should be considered for more effective disease control and that diets low in antioxidants may render individuals susceptible to tuberculosis.

Arginine

The Structure of the Arginine Repressor from Mycobacterium Tuberculosis Bound with Its DNA Operator and Co-Repressor, L-Arginine

Source: Journal of Molecular Biology 2009; 388(1): 85-97

Author: Cherney L.T., Cherney M.M., Garen C.R., James M.N.

Affiliation: Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.

Abstract: The biosynthesis of arginine is an essential function for the metabolism of Mycobacterium tuberculosis (Mtb) and for the metabolism of many other microorganisms. The arginine repressor (ArgR) proteins control the transcription of genes encoding the arginine biosynthetic enzymes; they belong to repressors having one of the most intricate oligomerization patterns. This study presents the crystal structure of the MtbArgR hexamer bound to three copies of the 20 base-pair DNA operator and to the co-repressor, L-arginine, determined to 3.3 A resolution. This is the first ternary structure of an intact hexameric ArgR in complex with its DNA operator. Two of the 20 base-pair DNA operators align in a unified double-helical structure, suggesting the possible presence of a double ARG box in the promoter region of the Mtb arginine operon. Two pairs of protomers bind to the unified double ARG box so that the two folded protomers bind to the central half-sites of the double ARG box, whereas the two extended protomers bind to the remote half-sites. The protomers of the third pair bound to the single DNA operator also have a folded and an extended conformation. A probable mechanism for arginine repression is suggested on the basis of this structure.

L-Arginine and Vitamin D: Novel Adjunctive Immunotherapies in Tuberculosis

Source: Trends in Microbiology 2008; 16(7): 336-344

Author: Ralph A.P., Kelly P.M., Anstey N.M.

Affiliation: International Health Division, Menzies School of Health Research, Building 58, Royal Darwin Hospital Campus, Casuarina, Northern Territory, Australia.

Abstract: Worsening drug resistance and the need for prolonged treatment in tuberculosis (TB) require innovative solutions including investigation of inexpensive, safe adjunctive immunotherapies. L-arginine, the precursor of nitric oxide, and vitamin D recently have elucidated mycobactericidal and immunomodulatory actions against TB and are deficient in people with TB. This study reviewes the potential of these agents as adjunctive TB immunotherapies and explores how comparative clinical trials might help clarify their relative importance in the human TB immune response. By enhancing mycobacterial killing in macrophages, L-arginine and vitamin D might have the potential to enable shorter duration of treatment, reduced infectivity and improved response in drug-resistant TB.

Crystal Structure of the Arginine Repressor Protein in Complex with the DNA Operator from Mycobacterium Tuberculosis

Source: Journal of Molecular Biology 2008; 384(5): 1330-1340

Author: Cherney L.T., Cherney M.M., Garen C.R., Lu G.J., James M.N.

Affiliation: Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Medical Sciences Building, Edmonton, Alberta, Canada.

Abstract: The arginine repressor (ArgR) from Mycobacterium tuberculosis (Mtb) is a gene product encoded by the open reading frame Rv1657. It regulates the L-arginine concentration in cells by interacting with ARG boxes in the promoter regions of the arginine biosynthesis and catabolism operons. This study presents a 2.5-A structure of MtbArgR in complex with a 16-bp DNA operator in the absence of arginine. A biological trimer of the protein-DNA complex is formed via the crystallographic 3-fold symmetry axis. The N-terminal domain of MtbArgR has a winged helix-turn-helix motif that binds to the major groove of the DNA. This structure shows that, in the absence of arginine, the ArgR trimer can bind three ARG box half-sites.

Nitric Oxide Production in the Exhaled Air of Patients with Pulmonary Tuberculosis in Relation to HIV Co-Infection

Source: BMC Infectious Disease 2008; 8: 146

Author: Idh J., Westman A., Elias D., Moges F., Getachew A., Gelaw A., Sundqvist T., Forslund T., Alemu A., Ayele B., Diro E, Melese E., Wondmikun Y., Britton S., Stendahl O., Schon T.

Affiliation: Department of Medical Microbiology, Faculty of Health Sciences, Linkoping University, 58185 Linkoping, Sweden.

Abstract: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. The aim of this study was to investigate levels of fractional exhaled air (FeNO) in relation to clinical symptoms and urinary NO metabolites (uNO). In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. The study concludes that in both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.

A Potential Role for Nitric Oxide Pathway in Tuberculous Pleural Effusion

Source: The International Journal of Tuberculosis and Lung Disease 2005; 9(3): 339-343

Author: Elgun S., Kacmaz B., Durak I.

Affiliation: Department of Biochemistry, School of Medicine, Ankara University, Sihhiye, Ankara, Turkey.

Abstract: Tuberculous pleural effusion leads to an immune response involving mainly immune and mesothelial cells. Nitric oxide (NO) produced by these cells may have antimycobacterial effects against Mycobacterium tuberculosis. The objective of this study was to investigate the possible role of NO in connection with the arginase enzyme, which controls the synthesis of NO through arginine depletion. Pleural fluid samples from 20 patients with tuberculous pleural effusion were used for arginase activity and NO level determination. Results were compared with those from 12 lung cancer, 12 pneumonia and 12 congestive heart failure (CHF) patients. The results show that pleural arginase activity in tuberculosis patients was found to be significantly decreased compared to lung cancer and pneumonia groups, while the NO level was higher in tuberculosis patients. All groups except the CHF group had significant correlations between NO level and white blood cell count. Arginase activity and red blood cell count correlated significantly in lung cancer and CHF groups. The study concludes that the arginine-NO pathway seems to be involved in the pathogenesis of tuberculous pleural effusion. Decreased arginase activity may cause arginine accumulation, which may then lead to increased NO synthesis by immune and mesothelial cells, reflecting a host defense mechanism.

Green Tea

Effect of Green Tea Extract (Catechins) in Reducing Oxidative Stress Seen in Patients of Pulmonary Tuberculosis on DOTS Cat I Regimen

Source: Phytomedicine 2010; 17(1): 23-27

Author: Agarwal A., Prasad R., Jain A.

Affiliation: Department of Microbiology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India.

Abstract: The present study was undertaken to assess the effect of crude green tea catechin in reducing the oxidative stress seen in patients of AFB positive pulmonary tuberculosis. A total of 200 newly diagnosed cases of AFB positive pulmonary tuberculosis who received CAT I regimen were enrolled consecutively from DOTS center. Out of 200 patients, 100 randomly selected patients received catechin (500 microg) with antitubercular treatment (ATT) (cases) and 100 received starch (500 microg) with ATT (control). Oxidative stress level in blood samples of cases and controls as compared at the time of enrollment and after one and four months of treatment. Oxidative stress was measured in terms of free radicals (lipid peroxidation, nitric oxide), enzymatic antioxidant (catalase, superoxide dismutase, glutathione peroxidase) and non enzymatic antioxidant (total thiol, reduced glutathione) levels. The findings suggest that crude catechin extract can play a definite role as adjuvant therapy in management of oxidative stress seen in pulmonary tuberculosis patients. More detailed studies are needed to document use of catechin in reducing the frequency and severity of side effects of treatment.

Combined Effect of Epigallocatechin Gallate and Triclosan on Enoyl-ACP Reductase of Mycobacterium Tuberculosis

Source: Biochemical and Biophysical Research Communications 2008; 368(1): 12-17

Author: Sharma S.K., Kumar G., Kapoor M., Surolia A.

Affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.

Abstract: Among the various inhibitors known for enoyl-acyl carrier protein (ACP) reductases, triclosan and green tea catechins are two promising candidates. The present study shows for the first time that epigallocatechin gallate (EGCG), a major component of green tea catechins, inhibits InhA, the enoyl-ACP reductase of Mycobacterium tuberculosis with an IC50 of 17.4muM. EGCG interferes with the binding of NADH to InhA. This study also demonstrates that EGCG increased the inhibitory activity of triclosan towards InhA and vice versa. Direct binding assay using [(3)H]EGCG and fluorescence titration assay support the spectrophotometric/kinetic inhibition data. The biochemical data has been explained by docking simulation studies.

Green Tea Polyphenol Inhibits Mycobacterium Tuberculosis Survival Within Human Macrophages

Source: The International Journal of Biochemistry and Cell Biology 2006; 38(4): 600-609

Author: Anand P.K., Kaul D., Sharma M.

Affiliation: Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Chandigarh, India.

Abstract: Lack of maturation of phagosomes containing pathogenic Mycobacterium tuberculosis within macrophages has been widely recognized as a crucial factor for the persistence of mycobacterial pathogen. Host molecule tryptophan-aspartate containing coat protein (TACO) has been shown to play a crucial role in the arrest of such a maturation process. The present study was addressed to understand whether or not polyphenols derived from green tea could down-regulate TACO gene transcription. And if yes, what impact TACO gene down-regulation has on the uptake/survival of M. tuberculosis within macrophages. The reverse-transcriptase polymerase chain reaction and reporter assay technology, employed in this study, revealed that the major component of green tea polyphenols, epigallocatechin-3-gallate had the inherent capacity to down-regulate TACO gene transcription within human macrophages through its ability to inhibit Sp1 transcription factor. We also found out that TACO gene promoter does contain Sp1 binding sequence using bioinformatics tools. The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, this study proposed that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection.

Protective Effect of Green Tea Extract Against the Erythrocytic Oxidative Stress Injury During Mycobacterium Tuberculosis Infection in Mice

Source: Molecular and Cell Biochemistry 2002; 236(1-2): 173-81

Author: Guleria R.S., Jain A., Tiwari V., Misra M.K.

Affiliation: Department of Microbiology, K. G's. Medical College, Lucknow, UP, India.

Abstract: The present study has been undertaken to monitor the extent of oxidative stress in mice infected with M tuberculosis and the role of crude green tea extract in repairing the oxidative damage. The mice were divided into three groups of 9 each; normal, infected-untreated and infected-treated. The infected group of animals exhibited significant enhancement of erythrocytic catalase and glutathione peroxidase activities along with elevated levels of erythrocytic total thiols and plasma lipid peroxidation as compared to normal animals. The infected group also exhibited significantly decreased activity of superoxide dismutase and levels of glutathione in erythrocytes. Upon oral administration of green tea extract for seven days the oxidative stress parameters were reverted back to near normal levels as evidenced by a fall in catalase, glutathione peroxidase, total thiol and extent of lipid peroxidation with concomitant increase in the levels of SOD and reduced glutathione in infected animals. The findings thus, portray that there is a high oxidative stress during early stages of tuberculosis and antioxidants such as green tea extract, can play a vital role by reducing stress through adjuvant therapy.

Nutrient Combination

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis

Source: The Journal of Infectious Disease 2008; 197(11): 1499-1505

Author: Villamor E., Mugusi F., Urassa W., Bosch R.J., Saathoff E., Matsumoto K., Meydani S.N., Fawzi W.W.

Affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.

Abstract: Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. This randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) was conducted in Dar es Salaam, Tanzania. In this study 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy were enrolled and monitored for a median of 43 months. The results show that micronutrients decreased the risk of TB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). A marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08) were also noted. Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. The study concludes that micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania.

Effect of Vitamin E and Selenium Supplementation on Oxidative Stress Status in Pulmonary Tuberculosis Patients

Source: Respirology 2008; 13(2): 294-298

Author: Seyedrezazadeh E., Ostadrahimi A., Mahboob S., Assadi Y., Ghaemmagami J., Pourmogaddam M.

Affiliation: Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz Azarbayegan Shargi, Iran.

Abstract: The present study evaluated the efficacy of vitamin E-selenium supplementation on oxidative stress in newly diagnosed patients treated for pulmonary tuberculosis (TB). A double-blind, placebo-controlled trial including patients with newly diagnosed TB was conducted. The intervention group (n = 17) received vitamin E and selenium (vitamin E: 140 mg alpha-tocopherol and selenium: 200 microg) and the control group (n = 18) received placebo. Both groups received standard anti-TB treatment. Assessment of micronutrient levels, oxidative markers and total antioxidant capacity were carried out at baseline and 2 months after the intervention. The results show that malondialdehyde levels were significantly reduced in the intervention group (P = 0.01), while there was minimal reduction in the control group. The mean plasma level of total antioxidants was increased significantly (P = 0.001) in both the intervention and the control groups. The study concludes that 2-month intervention with vitamin E and selenium supplementation reduces oxidative stress and enhances total antioxidant status in patients with pulmonary TB treated with standard chemotherapy.

The Effect of Multi-Vitamin/Mineral Supplementation on Mortality During Treatment of Pulmonary Tuberculosis: a Randomised Two-By-Two Factorial Trial in Mwanza, Tanzania

Source: The British Journal of Nutrition 2006; 95(4): 762-770

Author: Range N., Changalucha J., Krarup H., Magnussen P., Andersen A.B., Friis H.

Affiliation: National Institute for Medical Research, Muhimbili Research Station, PO Box 3436, Dar es Salaam, Tanzania.

Abstract: Malnutrition is common in pulmonary tuberculosis (TB), and may impair survival. The objective of this study was to assess effects of multi-vitamin/mineral (MVM) and zinc (Zn) supplementation during TB treatment on mortality. Patients diagnosed with sputum-positive pulmonary TB in Mwanza, Tanzania, were randomised, using a two-by-two factorial design, to Zn (45 mg) or placebo, and MVM (vitamins A, B, C, D, E, and selenium and copper) or placebo. Survival status was ascertained at the end of the 8-month TB treatment and supplementation period. Of 499 TB patients, 213 (43 %) had HIV. The mean weight gain at 7 months was 6.88 kg (95 % CI 6.36, 7.41). Zn and MVM combined, but neither alone (interaction, P=0.03), increased weight gain by 2.37 kg (95 % CI 0.91, 3.83), irrespective of HIV status. Among HIV co-infected patients, marginally significant effects of both MVM (RR 0.60; 95 % CI 0.34, 1.05) and Zn (RR 0.63, 95 % CI 0.37, 1.08) were seen, and MVM and Zn combined reduced mortality (RR 0.29; 95 % CI 0.10, 0.80; interaction ratio 0.52). In conclusion, supplementation with MVM, including Zn, during treatment of pulmonary TB may reduce mortality in those co-infected with HIV. A randomized trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding.

The Effect of Micronutrient Supplementation on Treatment Outcome in Patients with Pulmonary Tuberculosis: a Randomized Controlled trial in Mwanza, Tanzania

Source: Tropical Medicine & International Health 2005; 10(9): 826-832

Author: Range N., Andersen A.B., Magnussen P., Mugomela A., Friis H.

Affiliation: National Institute for Medical Research, Dar es Salaam, Tanzania.

Abstract: The aim of the study was to assess the effects of micronutrient supplementation on culture conversion in tuberculosis (TB) patients. DESIGN: The study was a randomized, double-blind placebo-controlled 2 x 2 trial of zinc and multi-micronutrient (MMN) supplementation in pulmonary TB patients in Tanzania. A total of 499 pulmonary TB patients were included in the trial after being confirmed sputum-positive by microscopy or culture. At 8 weeks, 25% were sputum-smear positive but only 11% were culture-positive (P<0.0001). Zinc had no effects on culture conversion. MMN increased weight gain by 0.78 kg [95% confidence interval (CI): 0.12--1.43] at week 8, while zinc supplementation had no effect. The effects of MMN and zinc did not interact and neither MMN nor zinc interacted with human immunodeficiency virus status, sex and culture-intensity at baseline. In conclusion neither zinc nor MMN supplementation had significant effects on culture conversion, but MMN supplementation increased weight gain in TB patients.

Micronutrient Malnutrition and Wasting in Adults with Pulmonary Tuberculosis With and Without HIV Co-Infection in Malawi

Source: BMC Infectious Disease 2004; 4(1): 61

Author: van Lettow M., Harries A.D., Kumwenda J.J., Zijlstra E.E., Clark T.D., Taha T.E., Semba R.D.

Affiliation: Johns Hopkins University School of Medicine, Baltimore, USA.

Abstract: Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. This study hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, alpha-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 micromol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids. These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

A Double-Blind, Placebo-Controlled Study of Vitamin A and Zinc Supplementation in Persons with Tuberculosis in Indonesia: Effects on Clinical Response and Nutritional Status

Source: The American Journal of Clinical Nutrition 2002; 75(4): 720-727

Author: Karyadi E., West C.E., Schultink W., Nelwan R.H., Gross R., Amin Z., Dolmans W.M., Schlebusch H., van der Meer J.W.

Affiliation: SEAMEO-TROPMED Regional Center for Community Nutrition, University of Indonesia, Jakarta, Indonesia.

Abstract: The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment. The goal of this study was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status. In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antituberculosis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment. The study concludes that vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion.

Selenium

Alterations in Serum Levels of Trace Elements in Tuberculosis and HIV Infections

Source: European Journal of Clinical Nutrition 2006; 60(5): 580-586

Author: Kassu A., Yabutani T., Mahmud Z.H., Mohammad A., Nguyen N., Huong B.T., Hailemariam G., Diro E., Ayele B., Wondmikun Y., Motonaka J., Ota F.

Affiliation: Department of Preventive Environment and Nutrition, Systems of Nutritional Sciences, Graduate School of Health Biosciences Research, The University of Tokushima, Tokushima, Japan

Abstract: The objective of this study was to evaluate serum concentrations of trace elements in tuberculosis (TB) patients with or with out human immunodeficiency virus (HIV) coinfection before and after anti-TB chemotherapy. A total of 155 TB patients, 74 of which were coinfected with HIV, and 31 healthy controls from Gondar, Ethiopia. Serum levels of copper, zinc, selenium and iron were determined using an inductively coupled plasma mass spectrometer from all subjects at baseline and from 44 TB patients (22 with HIV coinfection) at the end of an intensive phase of anti-TB chemotherapy. The results indicate that TB patients have altered profile of trace elements in their sera. This warrants the need for further investigations so that strategies for trace elements supplementation can be planned in addition to their potential as diagnostic parameters in monitoring responses to anti-TB chemotherapy.

Changes in Serum Selenium, Copper, Zinc Levels and Cu/Zn Ratio in Patients with Pulmonary Tuberculosis During Therapy

Source: Biological Trace Element Research 2003; 95(1): 65-71

Author: Ciftci T.U., Ciftci B., Yis O., Guney Y., Bilgihan A., Ogretensoy M.

Affiliation: Department of Pulmonology, Gazi University, Ankara, Turkey.

Abstract: The effectiveness and success of antituberculosis therapy is mainly measured by its ability to identify the organism in the sputum. In certain cases, available tuberculosis tests are not satisfactory and do not provide enough information on the effectiveness of antituberculosis therapy. Copper (Cu), zinc (Zn), and selenium (Se) are the essential elements that play a crucial role in the immune system. The serum levels of these elements vary in many diseases including tuberculosis. This study investigated whether the serum levels of Cu, Zn, and Se change during antituberculosis therapy. In the study 22 pulmonary tuberculosis cases were included that were newly diagnosed with positive sputum and 18 healthy subjects. At the beginning and 2 months after therapy, serum levels of Cu, Zn, and Se were measured by atomic absorption spectrometry. Despite Se and Cu levels not being affected during the treatment, the study found that there was a significant increase in the levels of Zn and a decrease in the Cu/Zn ratio. Serum Zn levels and the Cu/Zn ratio could be used as a valuable laboratory tool for the clinicians to assess response to therapy or effectiveness of the ongoing antituberculosis therapy.

Vitamin A

Vitamin A Deficiency and Other Factors Associated with Severe Tuberculosis in Timor and Rote Islands, East Nusa Tenggara Province, Indonesia

Source: European Journal of Clinical Nutrition 2009; 63(9): 1130-1135

Author: Pakasi T.A., Karyadi E., Wibowo Y., Simanjuntak Y., Suratih N.M., Salean M., Darmawidjaja N., van der Meer J.W., van der Velden K., Dolmans W.M.

Affiliation: University of Indonesia, Jakarta, Indonesia.

Abstract: Plasma zinc and vitamin A concentrations have been reported to be low in tuberculosis (TB) patients in some studies, although it is not clear whether this constitutes a risk for a more severe clinical presentation among TB patients. The acute phase reaction may also deplete zinc and vitamin A in the plasma. This study further examined these associations in a cross-sectional study among newly diagnosed sputum smear-positive TB patients in East Nusa Tenggara. The patients were categorized as either mild TB when Karnofsky Score (KS) > or =80 or severe TB (KS <80). Body mass index (BMI), mid upper arm circumference (MUAC), chest radiograph, and the results of hemoglobin, erythrocyte sedimentation rate, albumin, C-reactive protein (CRP), zinc and vitamin A in plasma were correlated with TB category. In conclusion, severe TB was associated with vitamin A deficiency. MUAC can be applied as a measure of TB severity.

Role of Vitamin A Supplementation in the Treatment of Tuberculosis

Source: The National Medical Journal of India 2007; 20(1): 16-21

Author: Mathur M.L.

Affiliation: Desert Medicine Research Centre, New Pali Road, Jodhpur 342005, Rajasthan, India

Abstract: Vitamin A deficiency has been commonly observed in patients with tuberculosis. Low serum retinol levels return to normal after antituberculosis treatment even when no supplements are provided. The deficiency of vitamin A observed in patients with tuberculosis might have contributed to the development of tuberculous disease in them. Alternatively, deficiency could be the result of loss of appetite, poor intestinal absorption, increased urinary loss of vitamin A or acute phase reaction in TB. Vitamin A deficiency lowers immunity while vitamin A supplementation reduces morbidity and mortality, particularly from measles and diarrhoea. Vitamin A supplementation also decreases the mortality rate in HIV-infected children and delays the progression of HIV disease in infected subjects. A higher incidence of lung cancer and increased mortality have been observed in smokers after beta-carotene supplementation. Zinc deficiency is also common in tuberculosis, which may impose a secondary vitamin A deficiency. Clinical trials have shown conflicting results regarding the effect of supplementation of vitamin A, alone or with other micronutrients, on time taken to sputum conversion in patients with pulmonary tuberculosis. Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in patients with tuberculosis, but clinical trials on such a combination are lacking.

Vitamin A Levels in Sputum-Positive Pulmonary Tuberculosis Patients in Comparison with Household Contacts and Healthy 'Normals’

Source: The International Journal of Tuberculosis and Lung Disease 2004; 8(9): 1130-1133

Author: Ramachandran G., Santha T., Garg R., Baskaran D., Iliayas S.A., Venkatesan P., Fathima R., Narayanan P.R.

Affiliation: Tuberculosis Research Centre (ICMR), Chennai, India.

Abstract: The objective of this study was to estimate serum vitamin A in pulmonary tuberculosis (PTB) patients at the start and end of anti-tuberculosis treatment. Serum vitamin A was estimated in 47 PTB patients (pre and post treatment), 46 healthy household contacts and 30 healthy 'normals'. The results show that mean serum vitamin A in patients at the start of treatment was 21.2 microg/dl, which was significantly lower than in household contacts (42.2 microg/dl) and healthy 'normals' (48.1 microg/dl). The vitamin A levels in patients increased following treatment. The study concludes that the low vitamin A levels observed in patients returned to normal at the end of anti-tuberculosis treatment without vitamin A supplementation.

Vitamin A Status of Patients Presenting with Pulmonary Tuberculosis and Asymptomatic HIV-Infected Individuals, Dar es Salaam, Tanzania

Source: The International Journal of Tuberculosis and Lung Disease 2003; 7(8): 804-807

Author: Mugusi F.M., Rusizoka O., Habib N., Fawzi W.

Affiliation: Department of Internal Medicine, Muhimbili University College of Health Sciences, Dar es Salaam, United Republic of Tanzania.

Abstract: Serum vitamin A was determined in a cross-sectional study of 100 HIV-positive and -negative tuberculosis patients and 144 blood donors. Tuberculosis patients were seen again after 2 months of treatment. Mean vitamin A was lowest among tuberculosis patients co-infected with HIV, and was lower among HIV-positive than -negative donors. Mean vitamin A rose significantly at 2 months in HIV-negative patients, and not in -positive patients. HIV infection was the strongest predictor of low vitamin A. Vitamin A deficiency is common in tuberculosis and HIV infection, particularly in those patients who are dually infected, and nutritional supplementation may be beneficial.

A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status.

Source: http://www.ncbi.nlm.nih.gov/pubmed/11916759

Author: Karyadi E, et al.

Affiliation: SEAMEO-TROPMED Regional Center for Community Nutrition, University of Indonesia, Jakarta, Indonesia.

Abstract: The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment. The goal of the study was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status. In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antituberculosis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment. At baseline, 64% of patients had a body mass index (in kg/m(2)) < 18.5, 32% had plasma retinol concentrations < 0.70 micromol/L, and 30% had plasma zinc concentrations < 10.7 micromol/L. After antituberculosis treatment, plasma zinc concentrations were not significantly different between groups. Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo. Sputum conversion and resolution of X-ray lesion area occurred earlier in the micronutrient group. Concluding, vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion.

Vitamin C

Effect of Ascorbic Acid and Emoxypine on the Dynamics of the Quantitative Roentgenological and Clinical Semiology Parameters During Infiltrative Tuberculosis of Lungs

Source: Eksperimental'naia i klinicheskaia farmakologiia 2009; 72(5): 22-26. [Article in Russian]

Author: Novoselov P.N.

Affiliation:

Abstract: Prospective, placebo-controlled randomized investigation has been performed to evaluate the effect of ascorbic acid and emoxypine on the dynamics of changes in the roentgenological and clinical pattern during infiltrative tuberculosis of lungs in comparison to the rate of Micobacterium tuberculosis eradication during the standard chemotherapy. The results show that it is expedient to include these substances in the standard chemotherapy scheme. The administration of ascorbic acid and emoxypine during the first 10 days of the standard schedule ensures accelerated resolution of tubercular infitrates and increased rate of closing of the tuberculous disintegration cavities. The use ofemoxypine accelerates the eradication of M. tuberculosis.

The Effectiveness of Ascorbic Acid and Emoxipin in Treatment of Infiltrative Pulmonary Tuberculosis

Source: Klinicheskaia meditsina 2007; 85(12): 55-58. [Article in Russian]

Author: Volchegorskii I.A, Novoselov P.N, Astakhova T.V.

Affiliation:

Abstract: The aim of this prospective placebo-controlled randomized study was to assess the effectiveness of ascorbic acid or emoxipin in the regimen of the therapy of infiltrative pulmonary tuberculosis. Emoxipin vs. ascorbic acid favored the eradication of tuberculosis mycobacteria. Both preparations decreased the blood level of the contra-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), shortened time to the closure of degeneration cavities in tubercular infiltrations, decreased the risk of the development of destructive forms, and lowered the need for surgical interventions for infiltrative pulmonary tuberculosis.

Ascorbic Acid in Blood Serum of Patients with Pulmonary Tuberculosis and Pneumonia

Source: The International Journal of Tuberculosis and Lung Disease 2004; 8(2): 263-266

Author: Bakaev V.V., Duntau A.P.

Affiliation: Novosibirsk Tuberculosis Hospital, Novosibirsk, Russia.

Abstract: Ascorbic acid plays a major role in pulmonary antioxidant defense. Sufficient amounts of ascorbic acid are necessary to maintain normal metabolic processes in the lung. This study measured the levels of ascorbic, dehydroascorbic and diketogulonic acids in blood serum of patients with pulmonary tuberculosis (PTB) and pneumonia. The serum levels of ascorbic acid were decreased in PTB and pneumonia, and those of dehydroascorbic acid were decreased in PTB, but not in pneumonia. The serum diketogulonic acid levels were not significantly changed in either PTB or pneumonia. The ratio of ascorbic to dehydroascorbic acid levels in serum were increased in PTB, but in pneumonia we observed a significant decrease in this index. The ratio of dehydroascorbic to diketogulonic acid in PTB was decreased, but in pneumonia this index did not significantly differ from the control value. Thus, in PTB the rate of ascorbic acid oxidation is decreased and the rate of dehydroascorbic acid oxidation is increased. By contrast, in pneumonia the rate of ascorbic acid oxidation is increased, but the rate of dehydroascorbic acid oxidation did not differ from control values.

Lipid Peroxidation, Vitamins C, E and Reduced Glutathione Levels in Patients with Pulmonary Tuberculosis

Source: Cell Biochemistry and Function 2004; 22(1): 19-22

Author: Vijayamalini M., Manoharan S.

Affiliation: Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India.

Abstract: The present study examined the relationship between lipid peroxidation and vitamin C, vitamin E and reduced glutathione levels in plasma, erythrocytes and erythrocyte membranes of pulmonary tuberculosis patients and an equal number of age-and sex-matched healthy subjects. Enhanced plasma, erythrocytes and erythrocyte membrane lipid peroxidation with concomitant decline in vitamin C, vitamin E and reduced glutathione levels were found in pulmonary tuberculosis patients. The elevated lipid peroxidation and decreased vitamin C, vitamin E and reduced glutathione levels indicate the potential of oxidative damage to erythrocytes and erythrocyte membranes of pulmonary tuberculosis patients.

Vitamin C and Other Compounds in Vitamin C Rich Food in Relation to Risk of Tuberculosis in Male Smokers

Source: Am Journal of Epidemiology 1999; 150(6): 632-41

Author: Hemila H., Kaprio J., Pietinen P., Albanes D., Heinonen O.P.

Affiliation: Department of Public Health, University of Helsinki, Finland.

Abstract: This study examined whether vitamin C rich food consumption and related vitamin C intake are associated with the risk of tuberculosis. The authors analyzed 167 incident cases of tuberculosis during a median follow-up time of 6.7 years in a clinical trial cohort of 26,975 Finnish men for whom they had baseline dietary data. A highly statistically significant inverse association between calculated vitamin C intake and the incidence of tuberculosis was found, but adjustment for non-dietary factors weakened the association to nonsignificant. Furthermore, the risk of tuberculosis decreased with increasing intake of fruits, vegetables, and berries independent of vitamin C intake. Subjects who had dietary vitamin C intake >90 mg/day and who consumed more than the average amount of fruits, vegetables, and berries had a significantly lower risk of tuberculosis (adjusted relative risk = 0.40; 95% confidence interval 0.24, 0.69). Associations between dietary vitamin C intake and occurrence of various diseases without proper control of confounding have often been interpreted as causal. These findings show that such associations can be confounded even by some other dietary components. Lower tuberculosis incidence in subjects who consumed more fruits, vegetables, and berries poor in vitamin C suggests that other compounds in such a diet may reduce the risk of tuberculosis.

Vitamin D

Vitamin D Receptor Genetic Polymorphisms and Tuberculosis: Updated Systematic Review and Meta-Analysis

Source: The International Journal of Tuberculosis and Lung Disease 2010; 14(1): 15-23

Author: Gao L., Tao Y., Zhang L., Jin Q.

Affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Abstract: Host genetic susceptibility has been suggested as one of the most important explanations for inter-individual differences in tuberculosis (TB) risk. The vitamin D receptor (VDR) gene has been studied as a candidate locus due to genetic polymorphisms that affects the activity of the receptor and subsequent downstream vitamin D-mediated effects. This study reviewed published studies on VDR polymorphisms and TB susceptibility up to 15 April 2009 and quantitatively summarised associations of the most widely studied polymorphisms (FokI, TaqI, ApaI and BsmI) using meta-analysis. A total of 23 eligible studies were included in this review. Heterogeneous results were observed, which may be partly explained by the differences between populations. Among Asians, the FokI ff genotype showed a pronounced positive association (OR 2.0, 95%CI 1.3-3.2), a significant inverse association was observed for the BsmI bb genotype (OR 0.5, 95%CI 0.4-0.8), and marginal significant associations were found for TaqI and ApaI polymorphisms. However, none of the polymorphisms was significantly related to TB among Africans or South Americans. The study concludes that the association of VDR polymorphisms with risk of TB observed in our analyses supports the hypothesis that vitamin D deficiency might play a role as risk factor during the development of TB.

Vitamin D in the Treatment of Pulmonary Tuberculosis

Source: The Journal of Steroid Biochemistry and Molecular Biology 2007; 103(3-5): 793-8.

Author: Martineau A.R., Honecker F.U., Wilkinson R.J., Griffiths C.J.

Affiliation: Centre for Health Sciences, Institute of Health Sciences Education, Barts and The London School of Medicine and Dentistry, London, United Kingdom.

Abstract: Vitamin D was used to treat tuberculosis in the pre-antibiotic era. New insights into the immunomodulatory properties of 1alpha,25-dihydroxy-vitamin D have rekindled interest in vitamin D as an adjunct to antituberculous therapy. This study describes the historical use of vitamin D in tuberculosis treatment; discusses the mechanisms by which it may modulate host response to infection with Mycobacterium tuberculosis; and reviews three clinical trials and ten case series in which vitamin D has been used in the treatment of pulmonary tuberculosis.

The Effect of Vitamin D as Supplementary Treatment in Patients with Moderately Advanced Pulmonary Tuberculous Lesion

Source: Acta Medica Indonesiana 2006; 38(1): 3-5

Author: Nursyam E.W., Amin Z., Rumende C.M.

Affiliation: Departement of Internal Medicine, Faculty of Medicine, University of Indonesia-dr.Cipto Mangunkusumo Hospital, Jakarta.

Abstract: The aim of this study was to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement, nutritional status, sputum conversion, and radiological improvement. Sixty seven tuberculosis patients visiting the Pulmonary Clinic, of Cipto Mangunkusumo Hospital, Jakarta, from January 1st to August 31st, 2001 were included in this study. The subjects were randomised to receive vitamin D (0.25 mg/day) or placebo in a double blind method, during the 6th initial week of Tb treatment. The rate of sputum conversion, complete blood counts, blood chemistry as well as radiologic examination were evaluated. There were more male patients than females (39:28), 78.7% were in the productive age group, 71.6% had low nutritional status, 62.4% with low education level, and 67.2% with low income. One hundred percent of the vitamin D group and only 76.7% of the placebo group had sputum conversion. This difference is statistically significant (p=0.002). In conclusion the sputum conversion had no correlation with the hemoglobin level, blood clotting time, calcium level, lymphocyte count, age, sex, and nutritional status. There were more subjects with radiological improvement in the vitamin D group.

Effect of Vitamin D3 on Phagocytic Potential of Macrophages with Live Mycobacterium Tuberculosis and Lymphoproliferative Response in Pulmonary Tuberculosis

Source: Journal of Clinical Immunology 2004; 24(3): 249-257

Author: Chandra G., Selvaraj P., Jawahar M.S, Banurekha V.V., Narayanan P.R.

Affiliation: Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, India.

Abstract: Immune responses are elicited through antigen presentation and recognition by macrophages and T-lymphocytes, respectively. The immunomodulatory effect of vitamin D(3) on macrophage phagocytic potential with live Mycobacterium tuberculosis, spontaneous and M. tuberculosis culture filtrate antigen induced lymphocyte responses were studied in pulmonary tuberculosis patients (PTBPs) ( n = 31) and normal healthy subjects (NHSs) ( n = 43). Vitamin D(3) at a concentration of 10(-7) M significantly enhanced the macrophage phagocytosis of live M. tuberculosis in normal subjects with low phagocytic potential (less than 10%) ( p = 0.015). No such increase was observed in PTBPs. Vitamin D(3) significantly decreased the spontaneous lymphoproliferative response ( p = 0.022) and increased the apoptosis of peripheral blood mononuclear cells in PTBPs ( p = 0.024). In normals, vitamin D(3) increased the spontaneous lymphoproliferative response. The present study suggests that exposure to vitamin D(3) increases the phagocytic potential and spontaneous lymphoproliferative response but brings down the antigen-induced response in normals. In tuberculosis, addition of vitamin D(3) has no significant effect on antigen-induced lymphoproliferative response. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) by virtue of the disease, which renders them inactive.

Vitamin E

Effect of Exogenous Vitamin E on Proliferation and Cytokine Production in Peripheral Blood Mononuclear Cells from Patients with Tuberculosis

Source: The British Journal of Nutrition 2008; 99(2): 224-229

Author: Hernandez J., Garibay-Escobar A., Mendoza-Mendoza A., Pinelli-Saavedra A., Valenzuela O.

Affiliation: Laboratorio de Inmunología, Centro de Investigacion en Alimentacion y Desarrollo, A.C., Sonora, Mexico

Abstract: Micronutrient deficiencies are frequently associated with tuberculosis (TB) worldwide. This study tested the effect of exogenous vitamin E on proliferation and cytokine production of peripheral blood mononuclear cells (PBMC) from TB patients and healthy purified protein derivative (PPD)+ volunteers. Proliferation was stimulated with mycobacterial antigen (PPD) and evaluated by the incorporation of tritiated thymidine in PBMC cultured with or without 50 microm-vitamin E for 6 d. Cytokine production (IL-2 and interferon (IFN)-gamma) was determined by intracellular cytokine staining and by ELISA in the supernatant of PBMC stimulated for 24 h with phytohaemagglutinin or PPD. The results show that culture with vitamin E increased (P < or = 0.05 ) the antigen-induced proliferation of PBMC in TB patients but not in healthy PPD+ volunteers. No significant changes in the number of cytokine-producing cells or in the production of IFN-gamma were observed with vitamin E treatment. These results indicate that vitamin E may enhance the antigen-specific in vitro response of PBMC from TB patients.

Oxidative Stress in Urogenital Tuberculosis Patients: a Predisposing Factor for Renal Stone Formation- Amelioration by Vitamin E Supplementation

Source: Clinica Chimica Acta 2004; 350(1-2): 57-63

Author: Srinivasan S., Pragasam V., Jenita X., Kalaiselvi P., Muthu V., Varalakshmi P.

Affiliation: Department of Medical Biochemistry, Dr. A.L. Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.

Abstract: Previous studies have shown that urogenital tuberculosis (GuTb) patients treated or untreated with regular anti-Tb regimen excrete comparatively high levels of urinary stone forming constituents than normal subjects. The present study was aimed to determine antioxidant status and lipid peroxidation of these individuals in order to assess their risk for kidney stone formation. GuTb patients and age-matched normal subjects were divided into four groups: I: normal subjects (n=60), II: GuTb patients a day before treatment (n=72), III: GuTb patients after treatment with isoniazid (300 mg), rifampicin (450 mg) and pyrazinamide (1.5 g) per day for 60 days (n=42), and IV: GuTb patients supplemented with vitamin E (200 mg/day) along with regular chemotherapy for 60 days (n=30). Blood was collected and tested for various markers of oxidative stress. The study concludes that vitamin E enhanced the antioxidant status of the plasma, thereby preventing membrane injury, consequently reducing the risk of stone formation in urogenital tuberculosis patients, who were treated with their routine anti-tuberculosis drug regimen.

Zinc

Status of Zinc in Pulmonary Tuberculosis

Source: Journal of Infection in Developing Countries 2009; 3(5): 365-368

Author: Ghulam H., Kadri S.M., Manzoor A, Waseem Q., Aatif M.S., Khan G.Q., Manish K.

Affiliation: Department Of Medicine, Government Medical College, Srinagar, Kashmir, India.

Abstract: The objective of this study was to examine the status of zinc as a micronutrient in pulmonary tuberculosis, in our population, with the aim to see the effectiveness of therapy. This prospective study includes 50 patients with pulmonary tuberculosis and 30 subjects as the control group. The patients were placed into three stages (1 to 3) on the basis of chest radiographic findings. Serum zinc levels were estimated before, during, and after completion of antituberculosis therapy. Statistically significant fall in serum zinc levels was seen with advanced age and disease, and the levels improved after initiation of antituberculosis therapy. The study concludes that estimation of serum zinc levels is an important tool in diagnosis and monitoring of response to treatment in pulmonary tuberculosis, and even a booster of the immunological mechanisms if instituted during the course of treatment.

Serum Zinc and Albumin Levels in Pulmonary Tuberculosis Patients With and Without HIV

Source: Japanese Journal of Infectious Disease 2008; 61(3): 202-204

Author: Ramakrishnan K., Shenbagarathai R., Kavitha K., Uma A, Balasubramaniam R., Thirumalaikolundusubramanian P.

Affiliation: Tuberculosis Research Centre, Madurai, India.

Abstract: Limited data are available on the relationship between nutritional status and pulmonary tuberculosis (PTB). Zinc plays a vital role in the immune status of the individual. The present study was carried out to estimate serum zinc and albumin levels in newly detected adult active PTB patients with (n = 20) and without (n = 20) HIV, and to compare them with the levels in controls (healthy family members; n = 20) who satisfied rigid selection criteria. Standard methods were adopted to collect an early morning fasting blood sample for zinc (by Atomic Absorption Spectrometer) and albumin (estimated by the bromocresol green method). The mean +/- SD for BMI, zinc and albumin among the controls, HIV positive and HIV negative patients were 19.6 +/- 0.6, 18 +/- 0.4 and 18.5 +/- 0.6 kg/m(2); 117.13 +/- 4.2, 53.9 +/- 8 and 65.5 +/- 9.8 microg/dL; and 4.1 +/- 0.6, 2.9 +/- 0.4 and 3.6 +/- 0.7 g/dL, respectively. All three parameters were significantly low in active PTB patients irrespective of HIV status, but more so in HIV-positive individuals. These changes may be attributable to nutritional factors, enteropathy and acute phase reactant proteins.

Impact of Anti-Tuberculosis Therapy on Plasma Zinc Status in Childhood Tuberculosis

Source: Eastern Mediterranean Health Journal 2007; 13(5): 1078-84

Author: Boloorsaz M.R., Khalilzadeh S., Milanifar A.R., Safavi A., Velayati A.A.

Affiliation: National Research Institute of Tuberculosis and Lung Disease, Massih Daneshvari Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran.

Abstract: This study compared plasma zinc levels in 15 children with active pulmonary tuberculosis, 15 malnourished children and 15 healthy children. Mean plasma zinc concentrations in children with tuberculosis (71.7 microg/dL) were not significantly different than the other 2 groups (72.5 and 76.9 microg/dL). The zinc status of the children with tuberculosis was evaluated after 2 months and 4 months of DOTS therapy. The serum zinc level during anti-tuberculosis therapy decreased after 1 month and then recovered to the initial level after 4 months of treatment.

Effect of Zinc on the Tuberculin Response of Children Exposed to Adults with Smear-Positive Tuberculosis

Source: Annals of Tropical Paediatrics 2002; 22(4): 313-319

Author: Cuevas L.E., Almeida L.M., Mazunder P., Paixao A.C., Silva A.M., Maciel L., Hart C.A., Coulter J.B.

Affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK

Abstract: The tuberculin test (PPD) is used frequently in the diagnosis of tuberculosis. PPD, however, relies on an intact cell-mediated immunity and infected children often have false negative results. This study assessed whether a single oral zinc supplement modifies the PPD induration size and its association with nutritional status in Brazilian children. Ninety-eight children below 15 years of age who had been exposed to adults with smear-positive pulmonary TB in 1998 were tested by PPD in 1998 and 2000. Children were randomised in 2000 to receive a single oral dose of zinc sulphate or a placebo at the time of administering the PPD. Forty-three (44%) children were PPD-positive in 1998 and 54 (55%) in 2000. A higher proportion of children were classified as PPD-positive in 2000 in the zinc-supplemented group (57.1%) than in the placebo group (53.1%). PPD indurations were larger in children receiving zinc (mean 18.5 and 15.5 mm in the zinc and placebo groups, respectively) (p < 0.03). Mean induration sizes in 2000 were larger in zinc-supplemented children, regardless of their nutritional status. This study demonstrates that zinc increases the PPD induration size in children irrespective of nutritional state. Zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a non-specific booster of immunological mechanisms (whether or not there is a deficiency).