Tuberculosis Depletes NAD+ (and Niacinamide May Be Able To Treat It)

Koveras

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As I was getting this post ready, I saw that haidut beat me to the punch by 3 years or so - but maybe the 2018 article that spurred this will answer @Giraffe 's question ("what's the mechanism?") in that thread


Pulling from instagram here

Vitamin B3 (Nicotinamide) for Tuberculosis (TB)?
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“…World Health Organization declared TB a "global health emergency" in 1993, and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aimed to save 14 million lives between its launch and 2015. A number of targets they set were not achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis.”
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“Treatment uses antibiotics to kill the bacteria. Effective treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective”
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Common drugs used to treat TB are Pyrazinamide and Isoniazide - which are actually derivatives of vitamin B3/nicotinamide, and it was known as early as 1945 that nicotinamide had an anti-TB effect
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“Nicotinamide monotherapy resulted in clinical improvement for up to 64% of M. tuberculosis–infected patients”
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“However, interest in nicotinamide as a treatment for TB faded rapidly when one of the foremost research groups of the day reported antagonism between nicotinamide and isoniazid when they were used together”
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Although derivatives, the drugs may have fundamentally different mechanisms of actions
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Most organisms require NAD+ (made from B3) and the drugs may kill TB by interfering with the bacteria’s ability to make it [side effects in humans may be for the same reason]
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If TB uses NAD+, how does taking it’s precursor (B3) benefit us?
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[2003] “Nicotinamide’s antimicrobial mechanism of action is not currently known. Its activity may come to be understood as that of an indirect antimicrobial that has primarily a PROHOST effect”
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[2018] Confirmed - TB infections deplete our own stores of NAD+, and that depletion cripples our immune system
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Many may have TB with no symptoms because of adequate diets in the ‘developed’ world (TB is also referred to as a ‘disease of POVERTY’)
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Future of health care might lie not in vaccines and antibiotics, but in curing poverty & malnutrition

"These implications may also apply to other bacterial and fungal pathogens that utilize NAD+ glycohydrolases, such as S. pyogenes (Chandrasekaran and Caparon, 2015) and the over 300 microorganisms encoding TNT homologs (Danilchanka et al., 2014)" (Pajuelo, D, 2018)

Chorine, V. (1945). Action of nicotinamide on bacilli of the type Mycobacterium. Compte Rendu de l'Academie des Sciences, 220, 150-151

Murray, M. F. (2003). Nicotinamide: an oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency virus. Clin Infect Dis, 36(4), 453-460. doi:10.1086/367544

Pajuelo, D., Gonzalez-Juarbe, N., Tak, U., Sun, J., Orihuela, C. J., & Niederweis, M. (2018). NAD(+) Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosis. Cell Rep, 24(2), 429-440. doi:10.1016/j.celrep.2018.06.042

Seiner, D. R., Hegde, S. S., & Blanchard, J. S. (2010). Kinetics and inhibition of nicotinamidase from Mycobacterium tuberculosis. Biochemistry, 49(44), 9613-9619. doi:10.1021/bi1011157

Zhang, Y., Shi, W., Zhang, W., & Mitchison, D. (2013). Mechanisms of Pyrazinamide Action and Resistance. Microbiol Spectr, 2(4), 1-12. doi:10.1128/microbiolspec.MGM2-0023-2013

Wikipedia contributors. (2018, August 23). Tuberculosis. In Wikipedia, The Free Encyclopedia. Retrieved 19:48, September 2, 2018, from Tuberculosis - Wikipedia
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sugarisgreat

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Tuberculosis (probably from all of the illegal immigration) outbreak in 3.....2.....1

First on Tucker: tuberculosis outbreak at Goldman Sachs in New York City


View: https://twitter.com/TuckerCarlson/status/1472024181353193474?s=20


 

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