Oranges may be the key to combating the tuberculosis pandemic, according to new findings that show vitamin C can kill drug-resistant strains of the bacteria. The study was published in today's edition of Nature Communications.
Dr. William Jacobs Jr. and his team at Albert Einstein College of Medicine stumbled upon the discovery while trying to figure out why Mycobacterium tuberculosis (TB), a lethal lung infection with 8.7 million new cases in 2011, becomes resistant to drugs in the first place.
One first-line medication for TB is isoniazid. This antibiotic was first used to treat TB in 1951, but less than a decade later, drug-resistant cases began to arise. Later research revealed that resistance could develop within a month of treatment.
In this study, the researchers observed that isoniazid-resistant strains fail to produce a nutrient called mycothiol.
"We hypothesized that TB bacteria that can't make mycothiol might contain more cysteine, an amino acid," said Jacobs
They predicted that adding cysteine and the TB-drug isoniazid to a petri dish filled with regular TB bacteria would cause them to become drug-resistant.
Instead, all of the bacteria died, which was startling.
"We ended up killing off the culture- something totally unexpected," said Jacobs.
The amino acid cysteine can sometimes behave as a "reducing agent" and elevate oxidative stress in cells. The scientists reasoned that this oxidative stress was damaging bacterial DNA and killing the TB.
To test this theory, they repeated the experiment with a different reducing agent - vitamin C. Not only did the isoniazid plus vitamin C combination kill TB, but vitamin C by itself was enough to destroy the bacteria.
Normal, multi-drug-resistant, and extensively drug-resistant strains were all killed by the citrus-related nutrient.
Further examination showed the lethal effects of vitamin C were due to the nutrient turning off genes that temper iron levels in the bacteria. High amounts of iron can provoke oxidative stress, which in turn damages the germ.
The authors were quick to note that all of the experiments were conducted in a dish, and further experiments in animal models and human trials are needed.
In humans, vitamin C levels in the blood and cellular tissue are tightly regulated, so it remains unclear if taking huge amounts of vitamin C would have an effect on TB infection. Indeed, this isn't the first study to identify vitamin C as a possible remedy for TB, with positive and negative results from multiple studies dating back to the 1930s.
"We don't know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial," said Jacobs. "It also helps that we know vitamin C is inexpensive, widely available and very safe to use. At the very least, this work shows us a new mechanism that we can exploit to attack TB."
Sources: Vilche C, Hartman T, Weinrick B, Jacobs Jr WR. Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nature Communications. 2013.
Keshavjee S, Farmer PE. Tuberculosis, Drug Resistance, and the History of Modern Medicine. N Engl J Med. 2012