View
3
Download
0
Category
Preview:
Citation preview
MICRONUTRITION FOR
TB PATIENT
Resti Yudhawati
Department of Pulmonology and Respiratory Medicine
Faculty of Medicine, Airlangga University
Dr. Soetomo Hospital Surabaya
Introduction
• TB remains a major global public health threat
• Over 1.4 million deaths reported in 2015
Estimated TB incidence rates, 2015
Global tuberculosis report, 2016
• Malnutrition and wasting are associated with TB
Ramakrishnan, 2008; Swaminathan, 2008
Introduction
• Approximately two-thirds of TB patients presenting with dramatic weight loss and malnutrition
• 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
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 JapanGupta, 2009; Karyadi E, 2000
Innate immune cells; macrophages,
neutrophils and dendritic
Adaptive immunity T-lymphocytes (CD-8, CD-4)
Increased production of cytokines
Ernst JD, 2012Kaufman SHE, 2010
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
TUBERCULOSIS
• Catabolisme
• Reduced food intake
• Increased losses
Wasting -- Nutritional deficiencies Micronutrition
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 dietCDC. 2015. Micronutrient Facts.
• 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
Low micronutrient status in TB patients
Summary of studies investigating micronutrient status of patients with pulmonary tuberculosis
Nutrient Findings Reference
Copper, zinc, selenium, iron
Ethiopia
↑ Mean copper, ↓ Mean zinc, ↓ Mean
selenium, ↓ Mean iron iKassu, 2006
Vitamin B6 (pyridoxine)
South Africa
90% low B6 at initiation tx, 100% ↓ B6
at one week Visser,. 2004
Vitamin A, E, zinc, selenium
Malawi
deficient in vitamin A, E, zinc and
selenium Van Lettow, 2005
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 1.3-6.5) Wilkinson , 2000
Vitamin C, Vitamin E, India ↓ Mean vitamin C and E in TB patients Vijayamalini, 2004
Selenium
Serum selenium levels ↓in pulmonary
tuberculosis l with and without
HIV/AIDS.
Ramakrishnan K,
2009
Zinc↓ levels of zinc in blood sample of TB
and TB- HIV infected patients
Ramakrishnan K,
2008, Bacelo AC,
2015
• Conclusively, the results indicated that patients with
tuberculosis have altered profile of vitamin (A, B6, C, D, E)
and trace elements (Selenium, zinc, iron ) in their sera
Role of micronutrients in TB
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 folatIron
ZincCopper
Selenium
Vitamin A
Vitamin B6
Vitamin B12
Vitamin D
Asam Folat
Zinc
Tembaga
Selenium
Maggini et al., 2007
Institute of Medicine National Academy of Scienec, 1999
Micronutrients and the
immune system
Micronutrients and the
immune system
Institute of Medicine National Academy of Scienec, 1999
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
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 bacilliBotella et al, 2011; Stensland et al, 2015
IRON
• The role of iron in the pathogencity, growth and metabolism of M. TB
depends on the acquisition of iron from host resources
• 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.
Meneghetti ET AL, 2016; Ratledge C. 2004
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
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 cathelicidin-mediated 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
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.TBCrowle AJ, 1989; Yamada et al, 2007
• 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
VITMIN B
Micronutrient supplementation
in TB
Mikronutrien DRI untuk laki-laki 19-70
tahun
DRI untuk perempuan 19-
70 tahun
Vit A 900 μg
(3000IU)
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
B6
(Pyridoxine)
1.3 - 1.7mg 1.3 - 1.5mg
B9(FolicAcid) 400 μg 400 μg
B12 2.4 μg 2.4 μg
Vit C 90 mg 75 mg
Vit D 15-20 μg 15-20 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 1000-1200 mg 1000-1200 mg
Manganese 2.3 mg 1.8 mg
Magnesium 410 – 420mg 310 – 320mg
Fe 8 mg 8-18 mg
Dietary Reference Intake (DRI). Bethesda: NIH; 2011
Dietary reference intake (DRI)
Vitamin A (DRI 2200-3000 IU/DAY)
VITAMIN A
+ ZINC
MULTI NUTRIENTS
• Armijos 2010 5000 IU/day
• Pakasi et al. 2010 5000 IU/day
• Lawson 2010 5000 IU/day
• Visser 2011 200.000 IU at day 1
• Range et al. 2005 5000 IU/day
• Semba 2007 5000 IU/day• Vilamor 8000 IU/day
• Praygod 2011 5000 IU/day
• Hanekom 1997 200.000 IU at day 0 and 1
• Pakasi et al. tahun 2010 5000 IU/ day.
Fails to reduce sputum conversion, improved
treatment outcomes, and body weight
ZINC
+ VIT A
MULTI NUTRIENTS
• Armijos 2010 50 mg/ day
• Lawson 2010 90 mg /week• Pakasi et al. 2010 15 mg/day
• Visser 2011 15 mg 5 x / week
• Range et al.2005 zinc 45 mg/day
• Lawson 2010 90 mg zinc/week
• Pakasi et al. 2010 15 mg zinc/day
• Range et al. 2005 45 mg/day
• Lawson 2010 90 mg/day
• Pakasi et al. 2010 15 mg/day
Fails to reduce sputum conversion, improved
treatment outcomes, and body weight
Zinc (DRI 8-11 mg/day)
VITAMIN A and Zinc
• Karyadi et al. 2002 Zinc 15 mg/hari + vitamin A 5000 IU/ day for 6 month
VITAMIN D vs
PLASEBO
VITAMIN D
MULTI NUTRIENTS
• Wesje 2008 100.000 IU at 5 and 8 months after the
start of treatment
• Range et al. 2005 5 µg/day
• Semba 2007 10 µg/day
• Morcos 1998 1000 IU/hi (8th initial week)
• Nursyam et al., 2006 250 µg/day (6th initial week )
Fails to reduce sputum conversion, improved
treatment outcomes, and body weight
Vitamin D (DRI 15-20 μg/day)
Nursyam et al., 2006 250 µg/day (6th initial week
show a significant difference in sputum conversion compared
with placebo. The percentage of radiological improvement
was also higher in the vitamin D group.
Supplementation with high doses of vitamin D (600,000 IU of
Intramuscular ) accelerated clinical, radiographic improvement in
all TB patients.
Salahuddin et al.2013
Vitamin D (High doses)
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
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 C
Safarian et al, 1990
VITAMIN E
• 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
SELENIUM
• 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
• Seyedrezazadeh E, 2007 vitamin E: 140 mg alpha-tocopherol and
Selenium: 200 microg
• 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.
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
Gangaidzo 2001
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
• Semba 2007
• Praygod 2011
• Vilamor 2008
• Metha 2010
Fails to reduce sputum conversion, improved
treatment outcomes, and body weight
MULTIVITAMIN and MINERAL
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
• 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
• Cochrane researchers After searching for relevant studies up to 4 February 2016, they included 35 relevant studies with 8283 participants.
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, 2013. Guideline: Nutritional Care and Support for Patient with Tuberculosis.
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, 2013. Guideline: Nutritional Care and Support for Patient with Tuberculosis.
Nutrition assessment -- BMI
• 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
Summary
35
Iron deficiency anemia
Normal Iron deficiency anemia Anemia of chronic disease
plasma Fe (mg/L) 70-90 30 30
Total iron binding
capacity
250-400 >450 <200
percent saturation 30 70 15
The content of Fe in
macrophages
++ - +++
serum ferritin 20-200 10 150
Serum transferrin
receptor
8-28 >28 8-28
Supandiman et al., 2014
Nutrition assessment
Adapted from WHO, 1995; WHO, 2000 and WHO, 2004
Recommended