Vitamin C Potentiates the Killing of Mycobacterium tuberculosis by the First-Line Tuberculosis Drugs Isoniazid and Rifampin in Mice

Antimicrob Agents Chemother. 2018 Feb 23;62(3):e02165-17. doi: 10.1128/AAC.02165-17. Print 2018 Mar.


The treatment of drug-susceptible tuberculosis (TB) is long and cumbersome. Mismanagement of TB treatment can lead to the emergence of drug resistance in patients, so shortening the treatment duration could significantly improve TB chemotherapy and prevent the development of drug resistance. We previously discovered that high concentrations of vitamin C sterilize cultures of drug-susceptible and drug-resistant Mycobacterium tuberculosis Here, we tested subinhibitory concentration of vitamin C in combination with TB drugs against M. tuberculosisin vitro and in a mouse model of M. tuberculosis infection. In vivo, we showed that the vitamin C level in mouse serum can be increased by intraperitoneal injection of vitamin C to reach vitamin C levels close to the concentrations required for activity in vitro Although vitamin C had no activity by itself in M. tuberculosis-infected mice, the combination of vitamin C with the first-line TB drugs isoniazid and rifampin reduced the bacterial burden in the lungs of M. tuberculosis-infected mice faster than isoniazid and rifampin combined in two independent experiments. These experiments suggest that the addition of vitamin C to first-line TB drugs could shorten TB treatment. Vitamin C, an inexpensive and nontoxic compound, could easily be added to the TB pharmacopeia to substantially improve chemotherapy outcome, which would have a significant impact on the worldwide TB community.

Keywords: isoniazid; mice; rifampicin; tuberculosis; vitamin C.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Disease Models, Animal
  • Drug Resistance, Bacterial
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Isoniazid / pharmacology*
  • Lung / drug effects
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred CBA
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Rifampin / pharmacology*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Multidrug-Resistant / pathology


  • Antitubercular Agents
  • Ascorbic Acid
  • Isoniazid
  • Rifampin