Why do people with tuberculosis lose weight

Univariate regression model 1 gave a crude assessment of the association between tuberculosis and plasma leptin concentration. The estimated proportion of variability in plasma leptin concentration explained multiple R 2 in model 2 was 0. Taken together, these findings are consistent with our hypothesis that tuberculosis-associated reductions in plasma leptin concentrations are mediated independently through a decreased percentage of body fat, inflammation, and possibly other, unidentified mechanisms.

Independent associations of various variables with plasma leptin concentration. Thus, factors indicate the proportional change in plasma leptin concentration adjusted for other variables in the model. The estimated intercepts in models 1 univariate and 2 multivariate were 3. The effect of antituberculous treatment on plasma leptin concentrations, appetite, nutritional status, and acute phase proteins was evaluated in 38 patients for whom blood test results were available after 2 months of treatment.

These patients reported a clear improvement of symptoms within 1—3 wk after start of treatment. There was no evidence that selection bias caused by missing data substantially affected the estimated effect of treatment on the change in plasma leptin concentration data not shown.

After 2 months of treatment, patients had a higher energy intake mean difference, kJ , body weight mean difference, 1. The relationship between plasma leptin concentrations and the ex vivo production of proinflammatory cytokines was investigated in 19 tuberculosis patients for whom data were available.

However, we could not directly demonstrate a significant association between changes in leptin concentrations and changes in cytokine production. Both inflammation and plasma leptin concentration were associated with loss of appetite in tuberculosis patients. Tuberculosis often leads to severe weight loss wasting , probably through the production of inflammatory mediators 2. Wasting, in turn, affects the inflammatory response, suppresses cellular immunity, and aggravates the outcome of tuberculosis In these complex relations between tuberculosis, nutritional status and the host immune response, leptin is a possible mediator.

In this study, plasma leptin concentrations were significantly suppressed in tuberculosis patients in Indonesia. Body fat mass was strongly correlated with plasma leptin concentrations, both in patients and controls. Results of multivariate regression analysis support the hypothesis that tuberculosis-associated reductions of plasma leptin were mediated independently by weight loss and inflammation. To our knowledge, there is one previous study on plasma leptin concentrations in tuberculosis patients In that report, leptin concentrations, as determined by RIA, were much higher than in ours.

The Turkish patients in that report had a much higher BMI, but it seems surprising to us that after treatment they had 3-fold higher leptin concentrations than control subjects. Loss of body fat mass could not entirely explain the observed low plasma leptin concentrations in tuberculosis patients in our study.

Body fat mass is the most important determinant of plasma leptin concentrations, but starvation, hormones including insulin and cortisol , as well as inflammatory mediators are able to modulate leptin production In sepsis patients, leptin levels were found to be elevated 23 — Attenuation of the acute phase response and proinflammatory cytokine production during antituberculous treatment was accompanied by an impressive increase of plasma leptin concentrations.

Of course, the acute inflammatory response in the animal and patient studies described above is different from the more chronic response in tuberculosis patients. The pattern of plasma leptin concentrations in weeks or months before diagnosis remains unknown, but one may hypothesize that the prolonged inflammatory response in tuberculosis down-regulates or exhausts leptin production.

In this study, multivariate analysis indicated that plasma leptin concentrations were associated with loss of appetite in tuberculosis. However, plasma leptin concentrations were substantially higher in control subjects without anorexia , and patients regained appetite during treatment, despite a substantial increase in plasma leptin concentrations.

Therefore, anorexia in tuberculosis seems to be determined to a much larger degree by inflammatory mediators e. Leptin signals the brain to decrease food intake, but so far no evidence has been found that anorexia in AIDS 26 , 27 and other inflammatory disorders is caused by increased leptin levels 28 , In fact, it may be the other way around; in both laboratory animals 30 and human subjects 8 , fasting induces falling leptin levels that evoke a number of adaptive responses, including suppression of metabolic rate 7.

Similarly, in tuberculosis, decreased energy intake may reduce leptin production. We did not measure energy intake, but it is likely to be lower among tuberculosis patients than healthy controls. Suppressed production of leptin may be detrimental for host defense against infections. In septic shock, mortality was found to be associated with decreased plasma leptin levels In an animal model, the absence 13 or starvation-induced down-regulation of leptin increased susceptibility to endotoxic shock, and leptin partially reversed this effect In addition, leptin reversed starvation-induced T-cell suppression Therefore, it may be hypothesized that decreased leptin production during active tuberculosis contributes to T-cell unresponsiveness.

We did not find a significant correlation between these two variables, which might be due either to the limited number of patients analyzed for cytokine production or to substantial intra- and interindividual variation of ex vivo cytokine production We were also unable to show a statistical association between leptin and tuberculin reactivity, but skin testing, which was only done before treatment, is a rather crude measurement.

Based on our data and results from previous studies, we hypothesize that in untreated tuberculosis, loss of body fat, reduced energy intake, and the host immune response reduce leptin production Fig. Because leptin is important for cell-mediated immunity, suppressed leptin concentrations may contribute to a worse outcome of tuberculosis, especially in cachectic patients. In theory, administration of leptin might benefit tuberculosis patients, but this is not feasible in a country like Indonesia.

Supplementation of micronutrients such as vitamin E 32 or zinc, which are known to increase leptin production 33 , might be a cost-effective alternative. Of interest, zinc has the additional advantage of stimulating appetite Hypothesized role of leptin in human tuberculosis. The inflammatory response in tuberculosis may suppress leptin production directly A , and through loss of body fat mass B and decreased energy intake C. Suppressed leptin production may contribute to decreased cell-mediated immunity.

In addition, wasting cachexia may contribute to a worse disease outcome through other, undefined mechanisms. Breda, The Netherlands. Shears P Epidemiology and infection in famine and disasters. Epidemiol Infect : — Google Scholar. Matthys P , Billiau A Cytokines and cachexia. Nutrition 13 : — J Nutr : — McMurray DN Impact of nutritional deficiencies on resistance to experimental pulmonary tuberculosis. Nutr Rev 56 : S — S Nature : — J Clin Endocrinol Metab 81 : — J Exp Med : — Science : — Am J Pathol : — N Engl J Med : — Durnin JV , Womersley J Body fat assessed from total body density and its estimation from skinfold thickness: measurements on men and women aged from 16 to 72 years.

J Immunol Methods : — J Appl Physiol 79 : — J Clin Immunol 13 : — Are they using them? Many people with TB believe that during their episodes of illness that they require special foods. A person with TB does not need a special diet, although they they should try and have a balanced diet. The goal of nutritional support is to restore body weight to the desirable range, with the emphasis being on regaining lost lean body mass. However, the effect of nutritional support on outcomes in patients with TB is unclear.

This page was last updated in October Author Annabel Kanabus. If you have found this page useful please tell other people about TBFacts. Nutritional care and support for patients with tuberculosis Nutritional care and support for patients with tuberculosis.

TB makes under nutrition worse. TB and Under Nutrition There is increasing evidence that under nutrition in patients with active TB is associated with an increased frequency and severity of disease and indeed a two to four fold increase in mortality. So TB and under nutrition can cause a vicious cycle of worsening disease and under nutrition.

TB Nutritional Assessment Because of the clear link between under nutrition and active TB, nutritional assessment and management are necessary parts of TB treatment and care for many people with TB. A complete nutritional assessment will normally consist of 3 parts which are: A clinical assessment, which includes a nutrition oriented history and a nutrition oriented examination An anthropometric assessment A dietary assessment.

TB Nutritional Counseling Nutritional counseling begins with the following practical rapid assessment consisting of: Nutritional status: Does the person look well nourished or not? Diet and preferences: What is the usual diet and any favorite foods?

Content of counseling Understanding the impact of TB on nutritional status and the importance of nutritional recovery. Tuberculosis patients often suffer from severe weight loss, which is considered to be immunosuppressive and a major determinant of severity and outcome of disease.

Because leptin is involved in weight regulation and cellular immunity, its possible role in tuberculosis-associated wasting was investigated. In an urban clinic in Indonesia, plasma leptin concentrations, indicators of adipocyte mass, appetite, C-reactive protein CRP , tuberculin reactivity, and cytokine response were measured in tuberculosis patients and healthy controls. Plasma leptin concentrations were lower in patients than in controls vs.