Suresh Gyan Vihar University International Journal of Environment, Science and Technology

Volume 4, Issue 2, August 2018, pp. 1-17

ISSN: 2394-9570

Changes in Nutritional Factors Affecting

Tuberculosis: A Systematic Review

Amarachi Ruth Anigbo1, Elizabeth Kanayo Ngwu2, Manjinder Kour3*

1Research Scholar, School of Applied Sciences , Suresh Gyan Vihar University, Jaipur, India

2Professor, Department of Nutrition and Dietetics, University of Nigeria, Nsukka, Nigeria

3Assistant Professor, School of Applied Sciences , Suresh Gyan Vihar University, Jaipur, India

*Corresponding author, email: manjinderkour1992@gmail.com

Abstract

Nutrition plays a major role in the management and prevention of tuberculosis(TB); this happens

in terms of the body immune response to the pathogenic organism. Nutrients like macro-nutrients

and micronutrients, vitamins, proteins, carbohydrates are associated with boosting immune

responses against pathogen mycobacterium tuberculosis causing tuberculosis. These nutrients

have an immunomodulatory effects in controlling exposure to infectious agents, the process of

inflammation and nutritional deficiency. When there is malnutrition, it increases the individual or

group of population’s susceptibility to progressive stages from infection to disease. This review

looks at various nutritional factors which includes the body mass index, weight, height, mid-arm

circumference which are nutritional indicators that show when an individual is healthy or

malnourished which leads to poor immune response that in turn affects an individual’s ability to

fight mycobacterium tuberculosis infection or disease. Some researches have been carried out to

show the relationship between nutritional factors and the roles they play in mycobacterium

tuberculosis infection and prevention. But, very few evidences in the literature has shown a

specific quantity of food that can alter the course of tuberculosis disease.

Keywords: Tuberculosis, Micronutrients, Macronutrients, Body mass Index, Mid Arm

Circumference.

2

1. INTRODUCTION

Tuberculosis is a bacterial disease caused by

Mycobacterium tuberculosis a condition in

which the body oxidizes an abnormally large

quantity of protein from foods rather than

using them for protein synthesis and leading

to a condition protein energy malnutrition

which is a high-risk factor that exposes an

individual or a group of persons to

tuberculosis [1]. According to the World

Health Organization (WHO), Tuberculosis

has been ranked number 9 among the world

leading cause of death [2], and these has been

attributed to so many factors, but specifically

to poor nutritional status especially among

the regions classified as high burdened

regions; of which India is ranked 5th among

the list of 30 countries.

Nutrition can be defined as the science of

eating food and the effects of food

components on the metabolism, health,

performance and disease resistance of human

and animals. Food is good, but an adequate

food is best for the immune system to

function properly so as to be able to defend

the entire body system when there are

exposures to infection. For an individual or

group of population to have adequate

nutritional intake, the six classes of food

which includes protein, carbohydrate, fats

and oil, vitamins and minerals have to be

taken in appropriate proportion. There is a

very close relationship between nutrition and

tuberculosis as deficiency of one or more

nutrients in the body for a long period of time

leads to the weakening of the immune system

which pre-disposes the individual or group of

population [3].

Nutritional indicators to show that a disease

condition like tuberculosis is present includes

body weight, height, body mass index, iron,

calcium, magnesium levels, vitamin D, K, C,

B12 levels. [4]. More so, when there is a pre-

existing condition like human

immunodeficiency virus (HIV), it plays a key

role in enhancing the rate of infection while

individual or group of population is exposed

to TB transmission; this could be termed as

exogenous factors. Certain factors like

socioeconomic, environmental and

behavioral are classified under exogenous

factors as they play a vital role in determining

the nutritional status of a population.

The objective of this study is to show

nutritional factors that positively or

negatively promote or prevent the occurrence

3

of tuberculosis infection individually or in a

group of population.

2. BODY MASS INDEX AND

TUBERCULOSIS

Body mass index (BMI) plays a very

important role in the well being of an

individual or a population [5]. Based on the

BMI an individual or group of individuals

can be classified as underweight, normal and

overweight Table1 [6]. A research conducted

in rural China with adults; showed that BMI

is associated with so many infections, and a

low BMI is associated with a susceptibility to

tuberculosis [7].

Classification BMI (kg/m2 )

Healthy Weight 18.5-24.9

Overweight 25-29.9

Obesity I 30-34.9

Obesity II 35-39.9

Obesity III 40 and above

Table 1: Source: Adapted from WHO 1995, WHO 2000 and WHO 2004. Accessed

22/12/2017

BMI has also been shown as a major tool in

determining the death rate among

tuberculosis patient’s in China, It was

observed that when there is malnutrition it

leads to underweight in an individual or a

group, that impairs or weakens the immune

system [9]. Further more a study conducted

in the United States showed that BMI, varied

amongst races and gender still using the

WHO BMI standards; Hispanic and men

from other races (which includes the

White/Caucasian, Black/African American,

Middle eastern, Indian, native American,

East-Asian, South-east Asian, pacific

islanders) had a high BMI of 26kg/m2 and

25kg/m2 respectively and the females had a

high body fat and a short height [10].

Undernutrition which results to a low BMI is

one of the major problem faced by TB

patients globally, especially in developing

countries and it is was discovered in the study

that one-third of the TB patients in Addis

Abba health Centre were undernourished,

and the prevalence of undernutrition among

the adults TB patients was high [11].

4

3. THE ROLE OF VITAMINS

IN TUBERCULOSIS

TB patients lack vital nutrients like vitamins,

causing them to get malnourished, and

placing them at a higher risk of getting

infection due to weakened immune response.

Vitamin as a dietary supplement has to be

taken exogenously because human beings

cannot synthesize vitamins or; if produced,

the concentration can’t be sufficient. Human

beings can synthesize Niacin (Vitamin B3)

and Vitamin D but lack the ability to

synthesize Thiamine (Vitamin B1),

Riboflavin (Vitamin B2), Pantothenic Acid

(Vitamin B5), Pyridoxine (Vitamin B6),

Biotin (Vitamin B7), Folate (Vitamin B9),

Cobalamin (Vitamin B12), Vitamin E,

Vitamin C, and Vitamin K [12]. Nutritional

supplements that has essential vitamins and

minerals could help patients to fight against

the disease by building up and strengthening

their immune response [13]. Vitamins always

have been considered an important

supplement that boosts immunity. Recent

studies have discovered the

antimycobacterial nature of vitamins[14]. In

one of the studies, it was discovered that

Vitamin D possesses antimycobacterial

properties which acts directly when added

into a growth medium [15]. The same was

also discovered for Vitamin A. Recently, a

study by Vilchèze et al. [16] Showed that

Vitamin C can inhibit M. tuberculosis

through hydroxyl radicals produced in

Fenton’s reaction. A common mechanism

used by bactericidal antibiotics to cause cell

death involves the generation of highly

reactive hydroxyl radicals through fenton’s

reaction. Hydroxyl radicals induce cell death

by damaging the DNA, which is in part due

to the oxidation of the guanine nucleotide

pool.

In the presence of reductants like vitamin C

in Fentons reaction, ferrous ions are produced

by reduction of ferric ions. Therefore vitamin

C has been discovered as a compound that

speeds up fentons reaction which makes

mycobacterium tuberculosis highly

susceptible to killing. In a cross-sectional

study carried out in Ethiopia, the

concentration of Vitamin C, Vitamin E, and

Vitamin A was found to be low in

Tuberculosis patients as compared to the

healthy controls [15]. Some reports states that

maintenance of an adequate level of Vitamin

D could be effective as a prophylactic method

against some respiratory tract infections [17].

In addition, a close relationship has been

found between Vitamin D levels and

Tuberculosis [13]. In fact, in the advent of

antibiotics, cod liver oil and exposure to

sunlight was used for Tuberculosis treatment.

5

Vitamin D activates production of

cathelicidin in white blood cells to kill TB

[18], Not only antimycobacterial properties

of vitamins but also essential biosynthetic

pathways operational in M. tuberculosis

involving vitamins are being studied from the

drug target perspective. Absence of

corresponding pathways in human beings

makes biotin and thiamin biosynthesis

pathways attractive drug targets [19].

Vitamins play diverse role in the infection

and pathogenicity of Tuberculosis. Studies

involving thiamin, biotin, Vitamin C, and

Vitamin D have gained significance

primarily due to their potency as drug targets

or because of their antimycobacterial

properties [20].

A. VITAMIN B1

Vitamin B1 also known as thiamine is an

essential micronutrient required for the

proper functioning of amino acid and

carbohydrate metabolic enzymes in its active

form, i.e., thiamin diphosphate [21-22]. It is

required for the biological activity of

pyruvate dehydrogenase, transketolase,

acetohydroxy acid synthase, and

2‑oxoglutarate dehydrogenase. M.

tuberculosis does not have thiamin

compensating mechanisms, making thiamin

biosynthetic mechanisms an attractive drug

target [23]. M. tuberculosis thiamin

phosphate synthase, a gene involved in the

synthesis of thiamin phosphate which is

further phosphorylated to the final product,

i.e., thiamin pyrophosphate in mycobacteria,

was screened bioinformatically for drug

targets by investigators. Results obtained

after virtual screening were tested in vitro and

one of the tested compounds showed potent

antimycobacterial activity having a low

inhibitory concentration (MIC) of 6 μg/ml

[24]. Further studies are required to validate

these findings and possibly reveal more

potential drug targets.

B. VITAMIN B7

Vitamin B7 also called biotin is essential for

growth and pathogenicity of M. tuberculosis.

It works as a cofactor in two key enzymes

required for fatty acid synthesis and

anaplerosis namely acyl CoA carboxylase

and pyruvate carboxylase [25]. These

enzymes are responsible for the metabolic

fixation of carbon dioxide. Biotin is an

indispensable vitamin for all living

organisms. However, its synthesis in plants,

and some fungi is limited. Like thiamin,

human beings are dependent on a dietary

supplement and gut microflora for their daily

uptake of biotin [26]. It has been suggested

that de novo biotin biosynthesis is necessary

6

for M. tuberculosis since it lacks biotin

transporters as discovered by genetic studies.

Moreover serum concentration of biotin is

very small in human beings to meet the

requirement needed [27]. Biotin is produced

with the help of enzymes BioF, BioA, BioD,

and BioB using pimeloyl‑CoA as a precursor

[28-30]. Synthesis of biotin from

pimeloyl‑CoA is well conserved in all the

biotin producing organisms.

C. VITAMIN C

Vitamin C also called ascorbic acid is an

essential micronutrient for human beings

which has to be taken as a dietary supplement

since humans cannot synthesize vitamin C

because of the mutation in the gene encoding

the enzyme gulonolactone oxidase

[31]. Vitamin C protects its host from

reactive oxygen and reactive nitrogen

intermediates generated during

mycobacterial infection [32]. For prevention

of common cold and influenza, Linus Pauling

in 1976 recommended 1–3 g/day of vitamin

C. Several studies have suggested the role of

vitamin C in the prevention and treatment of

TB by oral administration the vitamin.

Vitamin C deficiency has also been linked to

TB infection [33]. A study conducted on a

sample size of 1100 individuals diagnosed as

not having tuberculosis initially, correlated

their nutrition status with the susceptibility of

Tuberculosis development. Of all

individuals, 28 developed TB during the

course of the study and it was observed that

they had a less amount vitamin C

concentration [34]. It has also been shown

that Vitamin C acts as an activator for

inducing dormancy in M. tuberculosis.

Vitamin C induces DevR (DosR) regulation

which is responsible for the development of

dormancy in bacteria [35].

A study identifying antagonistic effects of

vitamin C when used with rifampicin and

isoniazid found some interesting results. It

was observed that there was reduction in the

colony forming units of wild type H37Rv

strain as well as drug-resistant strains, when

grown in the presence of vitamin C and

rifampicin at substantial Minimum Inhibitory

Concentration. Reduction in Colony Forming

Unit in wild type and drug-resistant strains

was also observed when vitamin C was tested

together with isoniazid. However, isoniazid-

vitamin C combination showed a weaker

effect against resistant strains as compared to

wild type H37Rv [36]. Narwadiya et al. have

shown an association between vitamin C

concentration and anti-TB properties of

medicinal plants [37]. Vitamin C reduces

ferric to ferrous ion which generates

superoxide, hydrogen peroxide, and hydroxyl

7

radicals in the presence of oxygen through

Fenton and Haber–Weiss reaction

[15]. These radicals damage the DNA and

lipids of M. tuberculosis leading to growth

impediment . Vitamin C is also believed to

reduce the level of guanosine 5'-diphosphate-

3'-diphosphate (ppGpp), a molecule thought

to be involved in growth regulation and stress

response in M. tuberculosis [38]. Recently it

was observed that water soluble vitamins of

which vitamin C is one, can prevent the

progression of a disease causing organism

because of its antioxidant activity. According

to Khameneh et al. 2016, vitamin c has shown

to selectively improve the antibacterial

activity of anti-tuberculosis drugs against

M.tuberculosis [39].

D. VITAMIN D

Vitamin D also called calciferol plays a role

in maintaining calcium homeostasis and bone

mineral density in human beings. It comes in

two major forms namely ergocalciferol

(Vitamin D2) and cholecalciferol (Vitamin

D3). This Vitamin is obtained either through

diet or exposure of epidermis to sunlight

(ultraviolet B radiation-UVB). However, its

role as a protective agent against various

diseases is being researched [40]. Studies

have found some relationship between

vitamin D deficiency and its susceptibility to

Tuberculosis since 1651, when the deficiency

of vitamins was found to be associated with

signs and symptoms of Tuberculosis for the

first time. Later, heliotherapy became a

common practice for patients with

Tuberculosis and this formed the basis of

treatment in sanatoria [41]. Meanwhile,

Stead et al. showed racial differences in the

incidence of Tuberculosis which was

associated with the levels of 25 hydroxy

Vitamin D [42]. Although conflicting results

which emerged from clinical trials, in one of

the studies carried out by Salahuddin et al.,

observed high doses of vitamin D

supplementation which enhanced clinical and

radiographic improvement in Tuberculosis

patients [43]. In a contrast, studies carried

out by Ralph et al.[44], and Daley et

al.[45] observed no significant improvement

in the culture conversion rate in vitamin D

supplemented patients. There is a debate

whether culture conversion rate can be a

parameter while studying the effect of

vitamin D supplementation. Tissue damage

prevention may be an appropriate method

during the study of vitamin D

supplementation effects [46].

Reports has shown that vitamin D

concentration in human beings depend on the

season and latitude which indirectly has a

8

relationship with Tuberculosis outbreak. A

study carried out at Birmingham having data

from 9739 patients over a period of 28 years

pointed to the fact that Tuberculosis

outbreaks increased by 24.1%, during the

winters there is low incidence of sunshine

with decreased vitamin D concentration

which led to higher Tuberculosis outbreak in

the winter season. A similar study was also

conducted in South Africa having the same

results [47]. Concentration of vitamin D in

humans depends on various factors that

include biosynthesis by human body,

pigmentation, latitude, dietary

supplementation, obesity, genetics, and

disease status. Deficiency of vitamin D (<50

nmol/l 25(OH)D) is a global problem, and

areas such as Middle East and South Asia

have severe deficiency which in turn may

increase the susceptibility to various diseases

[48].

Vitamins

Names

Scientific

Name

Solubility of

Vitamins

Food Sources

Plant Sources Animal Sources

Vitamin A

Retinol Fat Soluble Riped yellow

fruits, Yellow corn,

Carrots, pumpkin,

Squash, Spinach

Liver, Fish, Milk

Vitamin D Cholecalciferol Fat soluble Mushrooms Fish, Eggs, Liver

Vitamin

B1

Thiamine Water Soluble Oat meal, brown

rice, potatoes

Eggs, Liver

Vitamin

B7

Biotin Water Soluble Leafy green

vegetable, peanuts

Raw egg yolk, Liver

Vitamin C Ascorbic acid Water soluble Fruits and

vegetable

Liver

Table 2: Showing the sources of vitamins discussed in the Review Article [49].

4. PROTEIN-ENERGY

MALNUTRITION AND

TUBERCULOSIS

Proteins are large complex molecules that

play an important role in the body. They

perform mostly structural and regulatory

function in the tissues and organs. Proteins

9

are made up of thousands of smaller units

called amino acids which have been found to

have a link with tuberculosis infection.

According to WHO, protein energy

malnutrition is defined as an imbalance

between the supply of protein and energy and

the bodies demand for them to ensure optimal

growth and function. In india, Protein Energy

Malnutrition is one of the major concerns

among other healths disorders because of its

dire consequences ranging from physical to

cognitive growth and susceptibility to

infections [50]. The salvage cycle of

infection and undernutrition go hand in hand.

With inadequate dietary intake, the immune

response gets weaker and increases

susceptibility to infections [51]. A research

study conducted by the University of

California [UCLA] group of scientist

discovered that protein play a key role in

protecting people infected with

Mycobacteruim tuberculosis from

developing the active form of the disease.

The protein interleukin-32 which is a

protective protein was discovered to be one

biomarker that has an adequate host defense

against tuberculosis; it can induce killing of

the TB bacterium only in the presence of

vitamin D [52]. The in depth study of proteins

and its interactions has given a clearer

understanding with regards to tuberculosis

disease through proteomics study [53].

Undernutrion is observed with patients who

have tuberculosis infection and this is seen in

the form of wasting which is decrease in the

circulation of body protein mass, decreased

fat mass and a reduced protein and energy

intake. Protein energy malnutrition occurs as

a result of insufficient protein essential for

creating and regenerating body tissues; which

greatly compromises the body’s immune

functions [54]. Protein energy malnutrition

could be seen in the following forms (i) acute

malnutrition which is a precursor to wasting.

(ii) chronic Malnutrition which leads to

stunting [55]. Taking a critical observation at

the feeding patterns or behaviour of a

particular group of people; it can be deduced

that their feeding behaviours or pattern goes

a very long way in preventing malnutrition

and infection like tuberculosis [56]. Poverty

and income is more common to population

with lower income and even if malnutrition is

present in the upper income population, it is

limited to the milder forms [57]. There is a

disproportionate large number of

impoverished and socially excluded groups

in the society among the poor people, which

exposes them to further deprivable poverty,

food insecurity and undernutrition [58].

Though 26% of people live below the poverty

line in India, 46% of under three children are

10

suffering from undernutrition [59]. This

shows that the prevalence of poverty solely

cannot be responsible for undernutrition but

is an underlying cause of factors like

inadequate dietary intake, large family,

infection, unhygienic environment and

illiteracy which contributes to undernutrition

among low income group and when they are

undernourished, the immune system gets

weaken which pre-exposes them to getting

infected with tuberculosis.

Figure 1: Showing the cycle relationship between Protein Energy Malnutrition and Tuberculosis

When there is no steady source of income or

the income is very small, and the possibilities

of getting a well paid job is highly

competitive which is the case senario in the

indian setting, food insecurity sets in, the

people are not able to buy qualitative food that

Poverty

1

Worsened problem

of food insecurity

and nutrition

6

Active TB

7

Food Insecurity

2

Undernutrition

3

Reduced

Resistance to TB

4

Reduced inability

of people to work

5

Protein Energy Malnutrition and Tuberculosis Cycle

11

will be sufficient for the entire household.

When these continue for a long period of time,

undernutrition begins, members of the

household begin to lack some vital nutrients

that are required to build up the immune

system; causing the immune system to be

weak and become less resistant to primary

infections like tuberculosis that will want to

invade the imune system. Once the immune

system is weak, the strength to work and look

for sources to earn a living is greatly

compromised which worsens the problem of

food insecurity leading to a full

disease(tuberculosis) as a result of lack of

vital nutrients required by the body.

5. MICRONUTRIENTS AND

TUBERCULOSIS

Micronutrient deficiency happens as a result

of increased metabolic demands and

decreased intake of micronutrients which

worsen the disease and delay recovery by

supressing immune functions [60]. The

following micronutrients have shown to be of

great importance in improve immune

response when there is tuberculosis infection;

and these include Zinc, iron, copper, calcuim

and selenium [61]. Zinc- Various studies on

patients with tuberculosis had shown

significantly lower plasma zinc level than

those without tuberculosis, irrespective of

their nutritional status. There was significant

rise in zinc level at the end of six- months of

antituberculosis therapy (ATT). Thus, it may

be suggested that plasma zinc status is likely

a marker for monitoring the severity of

disease and response to therapy [62]. Zinc

supplementation of patients with pulmonary

tuberculosis helps to increase immunity and

thereby speed up the recovery process [63].

An adequate supply of zinc needs to be

ensured through foods such as seafood, meat,

seeds, and cooked dried beans, peas and

lentils [64]. Selenium- The essential trace

element selenium has an important function in

maintaining the immune processes and thus

may have a critical role in clearance of the

bacteria related to TB. Sea-foods and organ

meats are the richest food sources of

selenium. Other sources include muscle

meats, cereals and other grains, and dairy

products [65]. Anemia is highly prevalent

among adults with pulmonary tuberculosis. In

a study, concentration of hemoglobin was

lower in tuberculosis patients than that in

normal healthy subjects. There are two

reasons for the association of low iron status

and infection. One is that anemia which

results from chronic infection and the other is

that iron deficiency which increases the

susceptibility of a person or group of

individuals to infection like tuberculosis [66].

12

6. CONCLUSION

In summary there is a very close relationship

between macro nutrients and micro nutrients

and the prevention, treatment and control of

tuberculosis disease. Adequate nutrition plays

a vital role in building up the immune system.

If proper care and attention is paid to the

classes of food nutrients we consume, this

deadly disease tuberculosis will be a thing of

the past. A healthy immune system is

adequately fortified with food nutrients.

7. REFERENCE

1. Norman, J. T., Nelia, S. (2016).

Community Nutrition for Developing

Countries. AU Press, Athabasca

University, Canada and Unisa Press,

University of South Africa.

2. World Global Report for

Tuberculosis (2017)

http://www.who.int/tb/publications/gl

obal_r/eport/en/ Accessed

17/11/2017

3. https://www.collinsdictionary.com/di

ctionary/english/nutritionAccessed

27/11/2017

4. Guoyao, W.U. (2016). Dietary protein

intake and human health. Food Funct.,

7(3), 1251-65

5. Zhang, H., Li, X., Xin, H., Li H., Li,

M., Lu, W., Bai ,L., Wang, X., Liu,

J., Jin, Q., Gao, L. (2017).

Association Of Body Mass Index

With The Tuberculosis Infection: A

Population-Based Study Among

17796 Adults In Rural China. Sci.,

Rep., 8(7), 41933.

6. My idea

7. Yen, Y. F., Chuang, P. H., Yen, M.Y.,

Lin, S. Y., Chuang, P., Yuan, M. J.,

Deng, C. Y. (2016). Association of

Body Mass Index with Tuberculosis

Mortality: A Population-Based

Follow-Up Study. Medicine, 95(1),

2300-11.

8. World Health Organization. (2018).

Global Database on Body Mass Index

http://apps.who.int/bmi/index.jsp?intr

oPage=intro_3.html Accessed

30/09/2018.

9. Cai, J., Ma, A., Wang, Q., Han,

X., Zhao, S., Wang, Y., Schouten,

E.G., Kok, F.J. (2017). Association

between Body Mass Index and

Diabetes Mellitus in Tuberculosis

Patients In China: A Community

Based Cross-Sectional Study. Public

Health BMC, 17(1), 228-30

10. Bennett, D. E., Courval, J.

M., Onorato, I., Agerton, T., Gibson,

J. D., Lambert, L., McQuillan, G.

M., Lewis, B., Navin, T. R., Castro,

K. G. (2008). Prevalence of

Tuberculosis Infection in The United

States Population: The National

Health And Nutrition Examination

13

Survey, 1999-2000. Am. J. Respir.

Crit Care Med. 177(3), 348-55.

11. Berihun, D., Gezahegn, T., & Amare,

W. (2016). Prevalence and

Associated Factors of Undernutrition

among Adult Tuberculosis Patients in

Some Selected Public Health

Facilities of Addis Ababa, Ethiopia: A

Cross-Sectional Study. Nutrition

BMC Series, 3(7), 1-9.

12. Esposito, S., Lelii, M. (2015). Vitamin

D and Respiratory Tract Infections in

Childhood. BMC Infectious Diseases,

15, 487.

13. Ströhle, A., Wolters, M., Hahn, A.

(2011). Micronutrients at The

Interface Between Inflammation and

Infection – Ascorbic Acid and

Calciferol. Part 2: Calciferol and The

Significance of Nutrient Supplements.

Inflamm. Allergy Drug Targets, 10(1),

64-74.

14. Albahrani, A. A., & Greaves, R. F.

(2016). Fat-Soluble Vitamins:

Clinical Indications and Current

Challenges for Chromatographic

Measurement. The Clinical

Biochemist Reviews, 37(1), 27–47.

15. Vilchèze, C., Hartman, T., Weinrick,

B., & Jacobs, W. R.

(2013). Mycobacterium

Tuberculosis is Extraordinarily

Sensitive to Killing By a Vitamin C-

Induced Fenton Reaction. Nature

Communications, 1881(4), 1-10.

16. Greenstein, R. J., Su, L., Brown, S. T.

(2012). Vitamins A & D Inhibit The

Growth Of Mycobacteria in

Radiometric Culture. PLoS One, 7(1),

e29631.

17. Madebo, T., Lindtjørn, B., Aukrust,

P., Berge, R. K. (2003). Circulating

Antioxidants and Lipid Peroxidation

Products in Untreated Tuberculosis

Patients in Ethiopia. Am. J. Clin.

Nutr., 78(1), 117‑223

18. Patrick, J., McCullough, Douglas, S.,

Lehrer. (2018). Vitamin D, Cod Liver

Oil, Sunshine, and Phototherapy:

Safe, Effective and Forgotten Tools

For Treating and Curing Tuberculosis

Infections — A Comprehensive

Review. J. Steroid Biochem. Mol.

Biol., 177(1), 21-29.

19. Combs, G. F. Jr., McClung, J. P.

(2016). The Vitamins: Fundamental

Aspects in Nutrition and Health.

Cambridge, Massachusetts, United

States: Academic Press.

20. Du, Q., Wang, H., Xie, J. (2011).

Thiamin (Vitamin B1) Biosynthesis

and Regulation: A Rich Source of

Antimicrobial Drug Targets. Int. J.

Biol. Sci., 7(1), 41‑52.

21. Salaemae, W., Azhar, A., Booker, G.

W., Polyak, S. W. (2011). Biotin

Biosynthesis in Mycobacterium

Tuberculosis: Physiology,

Biochemistry and Molecular

Intervention. Protein Cell, 2(9),

691‑5.

22. Settembre, E., Begley, T. P., Ealick, S.

E. (2003). Structural Biology of

Enzymes of the Thiamin Biosynthesis

Pathway. Curr. Opin. Struct., Biol.

13(6), 739‑47.

14

23. Khare, G., Kar, R., Tyagi, A. K.

(2011). Identification of Inhibitors

against Mycobacterium Tuberculosis

Thiamin Phosphate Synthase, An

Important Target For The

Development of Anti‑TB Drugs.

PLoS One, 6(7), e22441.

24. Roje, S., (2007). Vitamin B

Biosynthesis in Plants.

Phytochemistry. Science Direct,

68(14), 1904‑21.

25. Mock, D. M., Malik, M. I. (1992).

Distribution of Biotin in Human

Plasma: Most of The Biotin is Not

Bound to Protein. Am. J. Clin. Nutr.,

56(2), 427‑32.

26. Hebbeln, P., Rodionov, D. A.,

Alfandega, A., Eitinger, T. (2007).

Biotin Uptake in Prokaryotes by

Solute Transporters with an Optional

ATP‑Binding Cassette‑Containing

Module. Proc. Natl. Acad. Sci. USA,

104(12), 2909‑14.

27. Rodionov, D. A., Mironov, A. A.,

Gelfand, M. S. (2002). Conservation

of the Biotin Regulon and the Bira

Regulatory Signal in Eubacteria and

Archaea. Genome Res., 12(10),

1507‑16

28. Lin, S., Cronan, J. E. (2011). Closing

in on Complete Pathways of Biotin

Biosynthesis. Mol. Bio. Syst., 7(6),

1811‑21.

29. Keer, J., Smeulders, M. J., Gray, K.

M., Williams, H. D. (2000). Mutants

of Mycobacterium

Smegmatisimpaired in

Stationary‑Phase Survival.

Microbiology, 146(9), 2209‑17.

30. Sassetti, C. M., Boyd, D. H., Rubin, E.

J. (2003). Genes Required for

Mycobacterial Growth Defined by

High Density Mutagenesis. Mol.

Micro. Bio., 48(1), 77‑84.

31. Ogata, K., Izumi, Y., Tani, Y. (1973).

The Controlling Action of Actithiazic

Acid on The Biosynthesis of Biotin-

Vitamers By Various

Microorganisms. Agric. Biol. Chem.,

37(5), 1079-85.

32. Nishikimi, M., Yagi, K. (1996).

Ascorbic Acid: Biochemistry and

Biomedical Cell Biology. Subcell

Biochem., 25(1), 17-35

33. Andosca, J. B., Foley, J. A. (1948).

Calcium Ribonate and Vitamin C (Nu

240-10) In the Treatment of

Tuberculosis. Dis. Chest., 14(2), 107-

14.

34. Getz, H. R., Long, E. R., Henderson,

H. J. (1951). A Study of the Relation

of Nutrition to the Development of

Tuberculosis. Influence of Ascorbic

Acid and Vitamin A. Am. Rev.

Tuberc. Pulm. Dis., 64(4), 381-93.

35. Taneja, N. K., Dhingra, S., Mittal, A.,

Naresh, M., Tyagi, J. S.

(2010). Mycobacterium

Tuberculosis Transcriptional

Adaptation, Growth Arrest and

Dormancy Phenotype Development is

Triggered By Vitamin C. PLoS One,

5(5), e10860.

36. Khameneh, B., Fazly, Bazzaz, B. S.,

Amani, A., Rostami, J., Vahdati-

15

Mashhadian, N. (2016). Combination

of Anti-Tuberculosis Drugs with

Vitamin C or NAC against

Different Staphylococcus

Aureus and Mycobacterium

Tuberculosis Strains. Microb.

Pathog., 93(1), 83-7.

37. Narwadiya, S. C., Sahare, K. N.,

Tumane, P. M., Dhumne, U. L.,

Meshram, V. G. (2011). In Vitro Anti-

Tuberculosis Effect of Vitamin C

Contents of Medicinal Plants. Asian J.

Exp. Biol. Sci., 4(2), 2-22

38. Mishra, A., Sarkar, D. (2015).

Qualitative and Quantitative

Proteomic Analysis of Vitamin C

Induced Changes in Mycobacterium

Smegmatis. Front, Microbiol., 6(1),

451-6.

39. Selvaraj, P., Harishankar, M., Afsal,

K. (2015). Vitamin D: Immuno-

Modulation and Tuberculosis

Treatment. Can. J. Physiol.

Pharmacol., 93(5), 377-84.

40. Facchini, L., Venturini, E., Galli, L.,

de Martino, M., Chiappini, E. (2015).

Vitamin D and Tuberculosis: A

Review on a Hot Topic. J.

Chemother., 27(3), 128-38.

41. Stead, W. W., Senner, J. W., Reddick,

W. T., Lofgren, J. P. (1990). Racial

Differences in Susceptibility to

Infection by Mycobacterium

Tuberculosis. N. Engl. J. Med.,

322(7), 422-7.

42. Salahuddin, N., Ali, F., Hasan, Z.,

Rao, N., Aqeel, M., Mahmood, F., et

al. (2013). Vitamin D Accelerates

Clinical Recovery From Tuberculosis:

Results Of The SUCCINCT Study

[Supplementary Cholecalciferol In

Recovery From Tuberculosis]. A

Randomized, Placebo-Controlled,

Clinical Trial of Vitamin D

Supplementation In Patients With

Pulmonary Tuberculosis'. BMC Infect.

Dis., 13(9), 22-24.

43. Ralph, A. P., Waramori, G.,

Pontororing, G. J., Kenangalem, E.,

Wiguna, A., Tjitra E, et al. (2013). L-

Arginine and Vitamin D Adjunctive

Therapies in Pulmonary Tuberculosis:

A Randomised, Double-Blind,

Placebo-Controlled Trial. PLoS One,

8(8), e70032.

44. Daley, P., Jagannathan, V., John, K.

R., Sarojini, J., Latha, A., Vieth, R., et

al. (2015). Adjunctive Vitamin D For

Treatment of Active Tuberculosis in

India: A Randomised, Double-Blind,

Placebo-Controlled Trial. Lancet.

Infect. Dis., 15(5), 528-34.

45. Cegielski, P., Vernon, A. (2015).

Tuberculosis And Vitamin D: What's

The Rest of The Story? Lancet. Infect.

Dis. 15(5), 489-90.

46. Martineau, A. R., Nhamoyebonde, S.,

Oni, T., Rangaka, M. X., Marais, S.,

Bangani, N. et al. (2011). Reciprocal

Seasonal Variation in Vitamin D

Status and Tuberculosis Notifications

in Cape Town, South Africa. Pro.

Natl. Acad. Sci. USA 108(47), 19013-

7.

47. Edwards, M. H., Cole, Z. A., Harvey,

N. C., Cooper, C. (2014). The Global

16

Epidemiology of Vitamin D Status. J.

Aging Res. Clin. Pract. 5(1), 148-58.

48. https://en.wikipedia.org/wiki/Vitamin

Assessed 08/1/2018

49. https://ghr.nlm.nih.gov/primer/howge

neswork/protein accessed 21/12/2017

50. National Nutrition Monitoring Bureau

(NNMB) Diet and nutritional status of

rural population, Technical report 21,

India. 2002. [Last retrieved on 2010

Oct 03]. Available from:

http://www.nnmbindia.org/NNMBR

EPORT2001.web.pdf . [Ref l

51. Rachel Champeau | August 20, 2014

http://newsroom.ucla.edu/releases/stu

dy-identifies-protein-that-helps-

prevent-active-tuberculosis-in-

infected-patients. Accessed

21/12/2017

52. https://proteomesci.biomedcentral.co

m/articles/10.1186/1477-5956-10-14.

Accessed 21/12/2017

53. Hood, M. L.H. (2013). A Narrative

Review of Recent Progress in

Understanding the Relationship

Between Tuberculosis and Protein

Energy Malnutrition. European

Journal of Clinical Nutrition, 67(1),

1122-1128.

54. World Health Organisation 2012.

(cited 10 October 2012). Fact File: 10

Facts on Nutrition. Available from

http://www.who.int/features/factfiles/

nutrition/facts/ en/index.html4.

55. Nutritional Status in Infancy and Early

Childhood. (2008). [Last retrieved on

2010 Oct 02]. Available from:

http://wcd.nic.in/research/nti1947/7.5

%20iycn%203.2.2008%20prema.pdf

56. Harishankar, Dwivedi, S., Dabral, S.,

B., Walia, D. K. (2013). Nutritional

Status of Children Under 6 Years of

Age. Indian J. Prev. Soc. Med., 35(1),

156–62.

57. Cohen, M., Tirado, C., Aberman, N.

L., Thompson, B. (2008). World Food

Insecurity and Malnutrition: Scope,

Trends, Causes and Consequences.

Rome: International Food Policy

Research Institute (IFPRI), Food and

Agriculture Organization of the

United Nations (FAO) 2008.

58. Mendelson S, Chaudhuri S. Child

malnutrition in India: Why does it

persist? Child in Need Institute (CINI)

[Last retrieved on 2010 Oct 07].

Available from:

http://www.cini.org.uk/childmalutriti

on.pdf

59. Shenkin, A. (2006). Micronutrients in

Health and Disease. Postgraduate

Medical Journal, 82(971), 559–567.

60. https://blog.ekincare.com/2016/03/23

/9-important-micronutrients-in-the-

diet-of-tuberculosis-patients/

Accessed 08/1/2018

61. Clinical Benefits of micronutrients in

Tuberculosis. http://www4.dr-rath-

foundation.org/research_news/article

s/20140707_health_information_tube

rculosis_edition20.html Accessed

008/1/2018.

62. Tuberculosis and

Nutrition.http://www.sun.ac.za/englis

h/faculty/healthsciences/nicus/Docu

ments/Files/Files/Fact_sheets/TB%20

and%20Nutrition.pdf Assessed

08/01/2018

17

63. https://www.eatforhealth.gov.au/food

-essentials/five-food-groups/lean-

meat-and-poultry-fish-eggs-tofu-

nuts-and-seeds-and Assessed

08/01/2018

64. Carolyn, D. B., Johanna, T. D.,

David, H. (2013). Handbook of

Nutrition and Food. CRC Press

65. http://www.scielo.br/scielo.php?scrip

t=sci_arttext&pid=S1806-

37132014000400403 Assessed

08/1/2018