MICRONUTRITION FOR TB PATIENT

Transcription

1 MICRONUTRITION FOR TB PATIENT Resti Yudhawati Department of Pulmonology and Respiratory Medicine Faculty of Medicine, Airlangga University Dr. Soetomo Hospital Surabaya

2 Global tuberculosis report, 2016 Introduction Estimated TB incidence rates, 2015 TB remains a major global public health threat Over 1.4 million deaths reported in 2015

3 Introduction Malnutrition and wasting are associated with TB Ramakrishnan, 2008; Swaminathan, 2008 Approximately two-thirds of TB patients presenting with dramatic weight loss and malnutrition Eddleston M, 2009, Fauci AS, 2008 Nutritional status is significantly lower in patients with active pulmonary tuberculosis in different studies in Indonesia, England, India, and Japan Gupta, 2009; Karyadi E, 2000 Malnutrition has been linked to impair immune responses Poor prognosis and is a major risk factor for mortality in TB patiens Chang SW, 2013; Lubart E, 2007

4 Innate immune cells; macrophages, neutrophils and dendritic Adaptive immunity T- lymphocytes (CD-8, CD-4) Increased production of cytokines Kaufman SHE, 2010 Ernst JD, 2012

5 TUBERCULOSIS Macrophages (resting state) activated state increased cellular turnover, essential nutrients, oxygen uptake, and protein synthesis Akiibinu MO, 2009; Edem VF, 2016; Kominsky Dj, 2010 Inflammatory and immune response cytokines (IL-1, IL-6, IL- 8, TNFα altered metabolism, Leptin, lipolytic and proteolytic, reduction in appetite Gupta, 2009, Paton NI, 2004, Sarraf P 1997, Verbon A, 1999 Catabolisme Reduced food intake Increased losses Wasting -- Nutritional deficiencies Micronutrition

6 Micronutrients Micronutrients are dietary components referred to as vitamins and minerals, only required by the body in small amounts Vital to development, disease prevention, and wellbeing. Micronutrients are not produced in the body and must be derived from the diet CDC Micronutrient Facts.

7 Low micronutrient status in TB patients Increased catabolism loss of appetite, Drug nutrient interactions Nausea and vomiting caused by anti-tb drugs Impaired absorption of nutrients Edem VF; 2015, Karyadi E, 2000; NICUS; 2007

8 Summary of studies investigating micronutrient status of patients with pulmonary tuberculosis Nutrient Findings Reference Copper, zinc, selenium, iron Mean copper, Mean zinc, Mean Kassu, 2006 Ethiopia selenium, Mean iron i Vitamin Conclusively, B6 (pyridoxine) the results 90% low B6 indicated at initiation that tx, 100% patients B6 with Visser, South tuberculosis Africa have at altered one week profile of vitamin (A, B6, C, D, E) Vitamin and A, E, trace zinc, selenium elements deficient (Selenium, in vitamin zinc, A, E, zinc iron and ) in their Van sera Lettow, 2005 Malawi selenium Vit A, zinc, Indonesia Mean vitamin A, zinc, in TB patients Karyadi, 2002 Vitamin D, England Vitamin D deficiency associated with active TB (OR 2.9; 95% CI ) Wilkinson, 2000 Vitamin C, Vitamin E, India Mean vitamin C and E in TB patients Vijayamalini, 2004 Selenium Serum selenium levels in pulmonary Ramakrishnan K, tuberculosis l with and without 2009 HIV/AIDS. Zinc levels of zinc in blood sample of TB and TB- HIV infected patients Ramakrishnan K, 2008, Bacelo AC, 2015

9 Role of micronutrients in TB

10 Summary of the sites of action of micronutrients on the immune system Epithelial barriers Cellular immunity Antibody production Vitamin A Vitamin C Vitamin E Zinc Vitamin A Vitamin B6 Vitamin B12 Vitamin C Vitamin D Vitamin E Asam folat Iron Zinc Copper Selenium Vitamin A Vitamin B6 Vitamin B12 Vitamin D Asam Folat Zinc Tembaga Selenium Maggini et al., 2007

11 Micronutrients and the immune system Institute of Medicine National Academy of Scienec, 1999

12 Micronutrients and the immune system Institute of Medicine National Academy of Scienec, 1999

13 Micronutrients Vitamins Thiamin (vitamin B1) Riboflavin (vitamin B2) Vitamin B6 (pyridoxine) Vitamin B12 Folate (vitamin B9) Choline Vitamin C Vitamin A Vitamin D Vitamin E Vitamin K Minerals Calcium Copper Iodine Iron Magnesium Manganese Phosphorus Potassium Selenium Sodium (Chloride) Zinc Cochrane Database of Systematic Reviews 2016

14 SELENIUM Reactive oxygen species and antioxidant activities in pulmonary tuberculosis patients enzymes glutathione peroxidase (GPx) Maintaining the immune processes and thus may have a critical role in clearance of mycobacteria Seyedrezazadeh E, 2007; Richie et al., 2012, Wu 6, 2016 ZINC Zinc is used by the cells of the immune system to destroy bacteria such as tubercle bacilli Botella et al, 2011; Stensland et al, 2015

15 IRON The role of iron in the pathogencity, growth and metabolism of M. TB depends on the acquisition of iron from host resources Meneghetti ET AL, 2016; Ratledge C M. TB ability in multiplication within host macrophages depends on the available iron. The iron deficiency in TB infected patients could be due to the M.TB iron consumption. Agarwal et 1l, 2016; Boelaert et al, 2007; Mwandumba et al, 2004 COPPER copper are components of an enzyme (superoxide dismutase) production of hydrogen peroxide, a potent factor of intracellular killing mechanism by phagocytes (macrophages and neutrophils) Edem et al, 2015 serum Cu/Zn ratio has been reported in patients with tuberculosis. The serum copper/zinc after anti-tuberculosis treatment. Mohan Gl, 2006; Sepehri et al, 2017

16 VITMIN D Vitamin D is known to be essential to M.TB containment and killing through activation of 25-hydroxyvitamin D receptors (VDRs) present on all immune cells. Binding of 1,25(OH)2 D3 activates VDRs and induces cathelicidinmediated killing of Mycobacteria. Liu et al, 2006; Liu et al, 2007 VITAMIN C and E Vitamins C (ascorbic acid) and E (alpha tocopherol) act as potent and the most important hydrophilic and lipophilic antioxidants respectively. Vitamin C scavenges superoxide radical, while vitamin E converts superoxide radical to less reactive forms Vijayamalini, M 2004

17 VITAMIN A Vitamin A helps in the normal function of immune cells and also enhances the synthesis essential cytokines with antitubercular activity Chakraborty et al, 2014 invivo study attenuates the severity of tuberculosis in vitro study Inhibition of multiplication M.TB Crowle AJ, 1989; Yamada et al, 2007 VITMIN B The direct association between TB and vitamin-b deficiency is not known Administration of Pyrazinamide, isoniazid vitamin B6 deficiency Vitamin-B supplementation is well recommended in order to avert several neurological complications in tuberculosis patients Chakraborty et al, 2014; Maggini et al, 2007

18 Micronutrient supplementation in TB

19 Dietary reference intake (DRI) Mikronutrien DRI untuk laki-laki tahun Vit A 900 μg (3000IU) DRI untuk perempuan tahun 700 μg (2200IU) B1 (Thiamine) 1.2 mg 1.1 mg B2 (Riboflavin) 1.3 mg 1.1 mg B3(Niacin) 16 mg 14 mg B mg mg (Pyridoxine) B9(FolicAcid) 400 μg 400 μg B μg 2.4 μg Vit C 90 mg 75 mg Vit D μg μg Vit E 15 mg 15 mg Selenium 55 μg 55 μg Copper 0.9 mg 0.9 mg Zinc 11 mg 8 mg Iodine 150 μg 150 μg Calcium mg mg Manganese 2.3 mg 1.8 mg Magnesium mg mg Fe 8 mg 8-18 mg Dietary Reference Intake (DRI). Bethesda: NIH; 2011

20 Vitamin A (DRI IU/DAY) VITAMIN A + ZINC MULTI NUTRIENTS Hanekom IU at day 0 and 1 Pakasi et al. tahun IU/ day. Armijos IU/day Pakasi et al IU/day Lawson IU/day Visser IU at day 1 Range et al IU/day Semba IU/day Vilamor 8000 IU/day Praygod IU/day Fails to reduce sputum conversion, improved treatment outcomes, and body weight

21 Zinc (DRI 8-11 mg/day) ZINC + VIT A MULTI NUTRIENTS Range et al mg/day Lawson mg/day Pakasi et al mg/day Armijos mg/ day Lawson mg /week Pakasi et al mg/day Visser mg 5 x / week Range et al.2005 zinc 45 mg/day Lawson mg zinc/week Pakasi et al mg zinc/day Fails to reduce sputum conversion, improved treatment outcomes, and body weight

22 VITAMIN A and Zinc Karyadi et al Zinc 15 mg/hari + vitamin A 5000 IU/ day for 6 month

23 Vitamin D (DRI μg/day) VITAMIN D vs PLASEBO VITAMIN D Morcos IU/hi (8th initial week) Nursyam et al., µg/day (6th initial week ) Nursyam et al., µg/day (6th initial week show Wesje a significant 2008 difference IU in at sputum 5 and conversion 8 months after compared the with start placebo. of treatment The percentage of radiological improvement was also higher in the vitamin D group. MULTI NUTRIENTS Range et al µg/day Semba µg/day Fails to reduce sputum conversion, improved treatment outcomes, and body weight

24 Vitamin D (High doses) Supplementation with high doses of vitamin D (600,000 IU of Intramuscular ) accelerated clinical, radiographic improvement in all TB patients. Salahuddin et al.2013 Administration of four doses of 2.5 mg vitamin D3 elevated serum 25- hydroxyvitamin D concentrations and reduced time to sputum culture conversion in participants with the tt genotype of the TaqI VDR polymorphism. Martineau et al.2011

25 VITAMIN C The efficacy of the antioxidative therapy in tuberculosis. Besides chemotherapeutic drugs, the administration of alpha-tocopherol, vitamin C and sodium nucleinate brings about higher rates of smear-negative cases and shorter period of cavity closure. VITAMIN E Safarian et al, 1990 Vitamin E supplementation, alone or in combination with other vitamins improve plasma levels of vitamin E, but this has not been shown to have clinically important benefits. Sinclair et al., 2011

26 SELENIUM Seyedrezazadeh E, 2007 vitamin E: 140 mg alpha-tocopherol and Selenium: 200 microg A 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 Highly recommended in pulmonary tuberculosis patients

27 IRON iron intake is associated with developing active tuberculosis infection and its mortality. M. TB ability in multiplication within host macrophages depends on the available iron Boelaert et al, 2007; Patel et al, 2016 dietary iron was associated with a 3.5-fold increase in the estimated odds of developing pulmonary TB and with a trend toward higher mortality among the patients with pulmonary TB. Gangaidzo 2001

28 MULTIVITAMIN and MINERAL A (2-3x DRI), vitamin B (1-10x DRI), vitamin C (1-5xDRI), vitamin D (1xDRI), vitamin E (1-10 x DRI), zinc (1-5 x DRI ), selenium (1-4x DRI) Range et al Semba 2007 Praygod 2011 Vilamor 2008 Metha 2010 Fails to reduce sputum conversion, improved treatment outcomes, and body weight

29 MULTIVITAMIN and MINERAL A (2-3x DRI), vitamin B (1-10x DRI), vitamin C (1-5xDRI), vitamin D (1xDRI), vitamin E (1-10 x DRI), zinc (1-5 x DRI ), selenium (1-4x DRI) Range et al. 2005

30 Cochrane researchers After searching for relevant studies up to 4 February 2016, they included 35 relevant studies with 8283 participants. Routinely providing multi-micronutrient supplements may have little or no effect on deaths in HIV-negative people with tuberculosis No studies have assessed the effect on quality of life Cohcrane; 2016

31 WHO. Guideline There is insufficient evidence whether multi micronutrients have a beneficial effect on mortality in TB HIV (-), but probably have little or no effect on mortality in TB HIV (+) No studies have assessed the effects of multi-micronutrients on TB cure, or completion of TB treatment. Multiple micronutrient supplements may have little or no efect on the proportion of TB patients remaining sputum positive during the first 8 weeks, and probably have no efect on weight gain during treatment. There is insufficient evidence whether routinely providing free food or energy supplements results in better TB treatment outcomes or improved quality of life WHO, Guideline: Nutritional Care and Support for Patient with Tuberculosis.

32 Micronutrient supplementation A daily multiple micronutrient supplement at 1 recommended nutrient intake should be provided in situations where fortifed or supplementary foods should have been provided in accordance with standard management of moderate undernutrition All pregnant women with active TB should receive multiple micronutrient supplements that contain iron and folic acid and other vitamins and minerals, For pregnant women with active TB in settings where calcium intake is low, calcium supplementation as part of antenatal care is recommended for the prevention of pre-eclampsia All lactating women with active TB should be provided with iron and folic acid and other vitamin and minerals WHO, Guideline: Nutritional Care and Support for Patient with Tuberculosis.

33 Nutrition assessment -- BMI

34 Summary Micronutrients status is significantly lower in patients with active pulmonary tuberculosis Micronutrients supplementation was shown to increase immune function There is insufficient evidence whether multi micronutrients have a beneficial effect on reduced duration of seputum conversion, improved treatment outcomes, quality of life and body weight in TB patient WHO recommended A daily multiple micronutrient supplement as standard management on moderate undernutrition, pregnant women, and lactating women with active TB Micronutrients supplementation providing Dietary Reference Intake

35 35

36 Iron deficiency anemia Normal Iron deficiency anemia Anemia of chronic disease plasma Fe (mg/l) Total iron binding capacity >450 <200 percent saturation The content of Fe in macrophages serum ferritin Serum transferrin receptor 8-28 > Supandiman et al., 2014

37 Nutrition assessment Adapted from WHO, 1995; WHO, 2000 and WHO, 2004