Vitamin C for Tuberculosis

By Alan R. Gaby, MD

Tuberculosis (TB) is an infectious disease caused by the bacterium, Mycobacterium tuberculosis. It is responsible for an estimated three million deaths per year worldwide. Pulmonary TB is the most common form of the disease, but the infection can also involve the central nervous system, gastrointestinal tract, genitourinary system, and other parts of the body. TB may be present as an active infection or as a latent, asymptomatic infection. Reactivation of the disease may occur after either an active or latent infection. An estimated two billion people have latent TB.

Treatment of TB usually involves a four-drug regimen of antibiotics such as isoniazid, rifampin, pyrazinamide, and ethambutol, typically administered for six months or longer. Multidrug-resistant TB (i.e., resistant to isoniazid and rifampin) requires an even longer treatment period and the use of second-line drugs that can have severe side effects. Antibiotic therapy is usually successful, although the prevalence of drug-resistant TB strains is increasing. Interventions that allow for shortening of the treatment period might prevent the development of drug resistance.

A recent study found that administration of vitamin C, as an adjunct to isoniazid and rifampin, shortened the recovery time in mice infected with M. tuberculosis. This study supports previous research related to vitamin C and TB and raises the possibility that vitamin C supplementation could improve outcomes in humans with TB.

Vitamin C and Tuberculosis

Research conducted in the 1930s found that guinea pigs fed a vitamin C-deficient diet had decreased resistance against TB infection. In addition, TB-infected guinea pigs had increased susceptibility to developing scurvy, suggesting that TB infection increases vitamin C requirements.^1,2 Studies in the 1940s found that plasma and urinary vitamin C levels were low in patients with TB. The severity of vitamin C deficiency increased with increasing severity of the disease. As much as 400 mg per day of supplemental vitamin C (4.4 times the current Recommended Dietary Allowance) was necessary in some TB patients to increase urinary vitamin C excretion to normal.^3,4

Maintaining adequate vitamin C status might increase resistance against TB infection in part by enhancing overall immune function. Administration of supraphysiological doses might provide additional benefit, since vitamin C at high concentrations acts directly against M. tuberculosis. In vitro, vitamin C at a concentration of 1 mg/dl had a bacteriostatic effect on M. tuberculosis, and at a concentration of 10 mg/dl or greater was bactericidal.⁵ In another study, the bactericidal concentration of vitamin C was higher: 35 mg/dl.⁶

The new research mentioned above included an in vitro study and a study in mice. In vitro, vitamin C a concentration of 17.6 mg/dl accelerated the killing of M. tuberculosis by the combination of isoniazid and rifampin and also accelerated the killing of M. tuberculosis by the combination of the second-line drugs, ofloxacin, kanamycin, and thioamide ethionamide.⁷ In the second part of the study, mice infected with M. tuberculosis were treated with isoniazid and rifampin. The mice also received or did not receive vitamin C intraperitoneally five days a week for four weeks at a dose of 3 g per kg of body weight. Although vitamin C had no activity by itself in infected mice, the combination of vitamin C with isoniazid and rifampin reduced the bacterial burden in the lungs faster than isoniazid and rifampin without vitamin C. At four weeks, the bacterial burden in the lungs was 93% lower in the vitamin C/isoniazid/rifampin group than in the control group.⁷

While the bacteriostatic concentration of vitamin C is within the physiologic range for healthy people (the normal serum vitamin C level is 0.2-2.0 mg/dl), many patients with TB would need to take a vitamin C supplement in order to bring their serum level up to 1.0 mg/dl. The serum vitamin C concentration that is bactericidal for M. tuberculosis is achievable only with parenteral administration of the vitamin. In healthy volunteers, the maximum tolerated oral dose of vitamin C (3 g every 4 hours) produced a serum vitamin C concentration of about 4 mg/dl, whereas intravenous administration of 0.5 g, 1.25 g, and 50 g of vitamin C produced peak serum levels of about 7 mg/dl, 14 mg/dl, and 80 mg/dl, respectively.^8,9

The available evidence supports the conclusion that most patients with TB should take a vitamin C supplement (such as 500 mg per day or more). In addition, clinical trials are warranted to determine whether parenteral administration of large doses of vitamin C would improve the results of conventional therapy.