NAC, Glutathione and Vitamin D to Support Immune Function

Over the course of the next couple weeks I will share with you some research on the pathophysiology of the flu virus, vaccinations, as well as research-based alternative options we can do to support ourselves during what seems to be increasingly more and more server annual outbreaks of the influenza virus.

~ N-Acetyl Cysteine & Glutathione ~

When we are infected with the flu virus our neutrophils (immune cells that respond to pathogenic infections) undergo[1] what is called “oxidative burst” (an increase in free radicals) as a means of controlling and eradicating the infection. Although the activity of the neutrophils is increased their overall function is decreased.[1] When exposed to the flu virus the neutrophils upregulate Toll-like receptors, which seem to decrease the function of the neutrophils.[2]

As the infection continues rapid viral replication, and consequent oxidative reactions of our neutrophils, increases the level of oxidative stress in the infected tissue. This vicious cycle results in greater levels of inflammatory cytokines and what we experience as the flu symptoms.

Glutathione is an antioxidant that is comprised of three amino acids; glutamate, cysteine, and glycine. Glutamine down regulates viral replication, [3-5] and protects the delicate lung tissue from the inflammation caused by oxidative reactions of our immune system’s attempt to clear the infection. [3]

The supplement N-Acetyl Cystine (NAC), being one of the precursors to intracellular glutathione can help to increase your own production of glutathione. NAC decreases oxidative reactions by scavenging free radicals that can damage the delicate cells of the lung. [6] When “pre-treated” with NAC inflammatory reactions can be decreased. [7]

In one mouse study oral glutathione was given to mice who where chemically depleted of their glutathione levels. With the oral dose the glutathione levels raised significantly in their kidney, heart, lung, brain, small intestine and skin but not in the liver. When they were given equivalent amounts of glutamate, cysteine, and glycine they did not have the same effect. [8]

~ Vitamin D ~

Is it a coincidence that the flu virus is most active during the late fall and winter months? “In 1981, R. Edgar Hope-Simpson proposed that a 'seasonal stimulus' intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza.”[9] The active form of vitamin D (1, 25(OH)2 D3) has a strong stimulatory affect on the immune system. It decreases cytokines and increases the ability of macrophages to actively scavenge pathogens, simulates expression of anti-microbial peptides in numerous types of immune cells as well as the cells lining the respiratory tract. [9] These antimicrobial peptides help to protect us from invading pathogens such as the flu virus.

Vitamin D modulates the immune response by decreasing virally induced inflammatory cytokines. In one study, although vitamin D did not clear the H1N1 infection from cell cultures, it “… significantly decreases the levels of H1N1-induced TNF-alpha (tumor necrosis factor-alpha), IFN-beta (interferon-beta), and IFN-stimulated gene-15 (ISG15).” [10] When you decrease these cytokines you can alter the course of the response to the infection and thus decrease the severity of a flu infection.

1. Cooper, J.A., Jr., R. Carcelen, and R. Culbreth, Effects of influenza A nucleoprotein on polymorphonuclear neutrophil function. J Infect Dis, 1996. 173(2): p. 279-84.
2. Lee, R.M., M.R. White, and K.L. Hartshorn, Influenza a viruses upregulate neutrophil toll-like receptor 2 expression and function. Scand J Immunol, 2006. 63(2): p. 81-9.
3. Yatmaz, S., et al., Glutathione peroxidase-1 reduces influenza a virus-induced lung inflammation. Am J Respir Cell Mol Biol, 2013. 48(1): p. 17-26.
4. Cai, J., et al., Inhibition of influenza infection by glutathione. Free Radic Biol Med, 2003. 34(7): p. 928-36.
5. Gutheil, W.G., E. Kasimoglu, and P.C. Nicholson, Induction of glutathione-dependent formaldehyde dehydrogenase activity in Escherichia coli and Hemophilus influenza. Biochem Biophys Res Commun, 1997. 238(3): p. 693-6.
6. Davreux, C.J., et al., N-acetyl cysteine attenuates acute lung injury in the rat. Shock, 1997. 8(6): p. 432-8.
7. Geudens, N., et al., N-acetyl cysteine pre-treatment attenuates inflammatory changes in the warm ischemic murine lung. J Heart Lung Transplant, 2007. 26(12): p. 1326-32.
8. Aw, T.Y., G. Wierzbicka, and D.P. Jones, Oral glutathione increases tissue glutathione in vivo. Chem Biol Interact, 1991. 80(1): p. 89-97.
9. Cannell, J.J., et al., Epidemic influenza and vitamin D. Epidemiol Infect, 2006. 134(6): p. 1129-40.
10. Khare, D., et al., Calcitriol [1, 25[OH]2 D3] pre- and post-treatment suppresses inflammatory response to influenza A (H1N1) infection in human lung A549 epithelial cells. Eur J Nutr, 2012.

In my ACA - Nutritional Synergy Update #5  I will continue discussing ... ginseng.