• David Sinclair, Katharine Abba, Liesl Grobler, and Thambu D Sudarsanam.
• International Health Group, Liverpool School of Tropical Medicine, Liverpool, UK. sinclad@liverpool.ac.uk.
• Cochrane Db Syst Rev. 2011 Jan 1(11):CD006086.

BackgroundTuberculosis 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.ObjectivesTo 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 MethodsWe 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 CriteriaRandomized 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 AnalysisTwo 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 ResultsTwenty-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' ConclusionsThere 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.

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