The first anti-tuberculosis drugs were developed 70 years ago and despite a significant decline of numbers of infected people, tuberculosis, a multi-organ infectious disease, still affects 2 billion people worldwide. In 2009, it caused the death of 1.7 million people. In the United States, the disease affects mainly risk groups, such as HIV positive individuals, homeless people and those who traveled to endemic areas. Treatment protocols for tuberculosis involve a combination of several drugs that target the bacteria, as well as vitamin B-6, which prevents adverse effects of one of the anti-tuberculosis medications.
Treatment of Tuberculosis
Until 1940, there was no specific treatment for tuberculosis. In 1944, the first studies showed that streptomycin was effective in treating experimental tuberculosis in animals. In 1952, isoniazid was also found to be effective against tuberculosis. Today, a combination of several anti-tuberculosis drugs is used to prevent development of bacterial resistance to anti-tuberculosis drugs.The drugs used routinely are isoniazid, rifampin, pyrazinamide and either ethambutol or streptomycin.
Isoniazid and Vitamin B-6 deficiency
Soon after isoniazid was employed in the management of tuberculosis, researchers noted that some patients develop peripheral neuropathy. This was characterized by symmetrical numbness in hands and feet which is described as "stocking-glove" distribution. This neuropathy was more severe in patients who received higher doses of isoniazid. At later stages, the neuropathy was characterized also by pain involving muscles and bones. In 1954, Biehl and Vilter of the University of Cincinnati College of Medicine investigated urine excretion of vitamin B group in the patients that received isoniazid. They found elevated levels of pyridoxine, also called vitamin B-6 that were more pronounced in patients on high doses of isoniazid. This suggested that isoniazid caused vitamin B-6 deficiency, which presented clinically as peripheral neuropathy.
Vitamin B-6 is essential for many biochemical processes. It is an important co-factor in metabolism of glucose, lipids and proteins, as well as in generation of hemoglobin, the protein in red blood cells that is critical for carrying oxygen from lungs to peripheral organs. Importantly, vitamin B-6 is also plays critical role in synthesis of several molecules of nervous system, such as histamine, serotonin, dopamine or gamma-aminobutyric acid.
Vitamin B-6 Prevents Isoniazid-Induced Neuropathy
In 1967, Beggs and Jenne from VA Medical Center in Minneapolis, Minnesota, showed there was a competitive relationship between isoniazid and vitamin B-6 and that these two molecules displace each other in biochemical reactions. Today, the neuropathy is prevented by vitamin B-6 routinely given at a dose of 10 to 50 mg per day during tuberculosis treatment. This is used particularly in patients at high risk for developing the neuropathy, such as patients with diabetes, pregnant and nursing women, patients with malnutrition or alcoholism, or acquired immunodeficiency syndrome.
- World Health Organization. Global tuberculosis control 2010.
- World Health Organization. Treatment of Tuberculosis: guidelines for national programmes
- J Am Med Assoc. Effects of isoniazid on pyridoxine metabolism. Biehl JP et al; December 1954, pages1549-52.
- J Bacteriol. Mechanism for the pyridoxal neutralization of isoniazid action of Mycobacterium tuberculosis. Beggs WH et al; October 1967, pages793-7.
- Int J Tuberc Lung Dis. Polyneuropathy, anti-tuberculosis treatment and the role of pyridoxine in the HIV/AIDS era: a systematic review. van der Watt JJ et al; Apr 2011