Nutritional supplements for people being treated for active tuberculosis.

Abstract

Background:
Tuberculosis and malnutrition are linked in a complex relationship. The infection may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there are no evidence-based nutritional guidance for adults and children being treated for tuberculosis.

Objectives:
To assess the effects of oral nutritional supplements (food, protein/energy supplements or micronutrients) on tuberculosis treatment outcomes and recovery in people on antituberculous drug therapy for active tuberculosis.

Search strategy:
We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, mRCT, and the Indian Journal of Tuberculosis to July 2011, and checked the reference lists of all included studies.

Selection criteria:
Randomized controlled trials comparing any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis.

Data collection and analysis:
Two authors independently selected trials, extracted data, and assessed the risk of bias. Results are presented as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CI). Where appropriate, data from trials with similar interventions and outcomes have been pooled. The quality of evidence was assessed using the GRADE methods.

Main results:
Twenty-three trials, with 6842 participants, were included.

Macronutrient supplementation
Five trials assessed the provision of free food, or high energy supplements, although none were shown to provide a total daily kilocalorie intake above the current daily recommended intake for the non-infected population.

The available trials were too small to reliably prove or exclude clinically important benefits on mortality, cure, or treatment completion. One small trial from India did find a statistically significant benefit on treatment completion, and clearance of the bacteria from the sputum, but these findings have not been confirmed in larger trials elsewhere (VERY LOW quality evidence).

The provision of free food or high-energy nutritional products probably does produce a modest increase in weight gain during treatment for active tuberculosis (MODERATE quality evidence). Two small studies provide some evidence that physical function and quality of life may also be improved but the trials were too small to have much confidence in the result (LOW quality evidence). These effects were not seen in the one trial which included only human immunodeficiency virus (HIV)-positive patients.

Micronutrient supplementation
Five trials assessed multi-micronutrient supplementation in doses up to ten times the dietary reference intake, and 12 trials assessed single or dual micronutrient supplementation.

There is insufficient evidence to judge whether multi-micronutrients have a beneficial effect on mortality in HIV- negative patients with tuberculosis (VERY LOW quality evidence), but the available studies show that multi-micronutrients probably have little or no effect on mortality in HIV-positive patients with tuberculosis (MODERATE quality evidence). No studies have assessed the effects of multi-micronutrients on cure, or treatment completion.

Multi-micronutrient supplements may have little or no effect on the proportion of tuberculosis patients remaining sputum positive during the first eight weeks (LOW quality evidence), and probably have no effect on weight gain during treatment (MODERATE quality evidence). No studies have assessed quality of life.

Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, plasma levels of zinc, vitamin D and E, and selenium may be improved by supplementation during the early stages of tuberculosis treatment, but a consistent benefit on tuberculosis treatment outcomes or nutritional recovery has not been demonstrated.

Authors' conclusions:
There is insufficient research to know whether routinely providing free food or energy supplements results in better tuberculosis treatment outcomes, or improved quality of life. Further trials, particularly from food insecure settings, should have adequate sample sizes to identify, or exclude, clinically important benefits.

Although blood levels of some vitamins may be low in patients starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing at or above recommended daily amounts has clinical benefits.

Plain language summary
Researchers in The Cochrane Collaboration conducted a review of the effects of nutritional supplements for people being treated for tuberculosis. After searching for relevant studies, they identified 23 relevant articles. Their findings are summarized below.

What is tuberculosis and how might nutritional supplements work?

Tuberculosis is a bacterial infection which most commonly affects the lungs. Most people who get infected never develop symptoms as their immune system manages to control the bacteria. Active tuberculosis occurs when the infection is no longer contained by the immune system, and typical symptoms are cough, chest pain, fever, night sweats, weight loss, and sometimes coughing up blood. Treatment is with a combination of antibiotic drugs, which must be taken for at least six months.

People with tuberculosis are often malnourished, and malnourished people are at higher risk of developing tuberculosis as their immune system is weakened. Nutritional supplements could help people recover from the illness by strengthening their immune system, and by improving weight gain, and muscle strength, allowing the patient to return to an active life.

Good nutrition requires a daily intake of macronutrients (carbohydrate, protein, and fat), and micronutrients (essential vitamins and minerals).

What the research says: Effect of providing nutritional supplements to people being treated for tuberculosis

We currently don't know if providing free food to tuberculosis patients, as hot meals or ration parcels, reduces death or improves cure. Providing free food probably does improve weight gain during treatment, and may improve quality of life but further research is necessary.

We don't know if vitamins reduce death in HIV-negative people but they probably don't work in HIV-positive people with tuberculosis. No studies have assessed whether vitamins improve tuberculosis cure. Vitamins probably don't improve weight gain, and no studies have assessed their effect on quality of life.

Citation

Sinclair, D.; Abba, K.; Grobler, L.; Sudarsanam, T. D. Nutritional supplements for people being treated for active tuberculosis. Cochrane Database of Systematic Reviews (2011) Issue 11, Art. No. CD006086. [DOI: 10.1002/14651858.CD006086.pub3]

Nutritional supplements for people being treated for active tuberculosis.

Published 1 January 2011