Mice injected with high-dose vitamin C while treated with the drugs isoniazid and rifampicin showed substantially lower bacterial burden in the lungs after four weeks, compared with those given the pharmaceutical treatment alone, say the team writing in the journal Antimicrobial Agents and Chemotherapy.
A similar effect was observed when mice were infected with higher initial levels of Mycobacterium tuberculosis (Mtb), according to the research team from the Albert Einstein College of Medicine, Bronx, NY.
In this case, the additional benefit of combined treatment took six weeks to appear. However, once again, the scientists found an order of magnitude lower level of lung bacterial burden in the vitamin C injected mice.
"Our study shows that the addition of vitamin C to TB drug treatment potentiates the killing of Mtb and could shorten TB chemotherapy," said lead researcher Professor William R. Jacobs, Jr.
This is significant because treatment of drug susceptible tuberculosis takes six months, "resulting in some treatment mismanagement, potentially leading to the emergence and spread of drug-resistant TB," added Jacobs.
The results in live mice were a follow-up to initial in vitro experiments. The laboratory studies also showed that vitamin C, used in combination with three second-line drugs (used in treatment of multi drug-resistant (MDR) TB) shortened the sterilisation time of the infection.
High- doses and tolerability
The mice were injected with doses of 3 grams/ kilogram (g/kg), which was found to be effective and tolerable.
Whether such doses are tolerable in humans needs further investigation. An early trial, which used a dose of 15 g/day for around 6 months in terminally ill TB patients showed no adverse effects.
Nevertheless, as the researchers emphasise, vitamin C alone has no effect on TB infection burden and the potential benefit is as an adjunct therapy to the front-line drugs.
The scientists believe that vitamin C may work by stimulating the respiration of the Mtb cells, making them more vulnerable to the action of isoniazid and rifampicin. Vitamin C co-therapy may also reduce the formation of ‘persisters’ – a small fraction of the Mtb population which is treatment resistant. Persisters are thought to involved with the development of drug-resistant mutant TB strains.
Further work
"Vitamin C is known to be safe and our current mouse studies suggest that vitamin C could enhance TB chemotherapy," advocated Jacobs. "A clinical trial of vitamin C with TB chemotherapies could demonstrate that such an adjunct therapy could reduce patients' exposure to toxic TB drugs and also reduce the spread of TB from infected individuals."
Combined therapy could potentially result in “a reduction in the incidences of both drug-resistance development and disease relapse,” Jacobs proposed.
Source: Antimicrobial Agents and Chemotherapy
Accepted manuscript posted online 3 Jan 2018, doi: 10.1128/AAC.02165-17
“Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice”
Authors: Catherine Vilchèze, John Kim, and William R. Jacobs Jr.