N-Acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)

N-Acetyl cysteine (NAC) is used as a mucolytic in the treatment of respiratory diseases and in the treatment of acetaminophen overdose. It also restores glutathione levels and consequently antioxidant defense mechanisms. In mice with bleomycin-induced pulmonary fibrosis NAC has been shown to reduce lung collagen content. In endothelial cells from bovine pulmonary artery NAC, at 10 mM in combination with glutathione 10 mM and cysteine 5 mM, inhibited the activity of transforming growth factor beta (TGFbeta). In rat hepatic stellate cells NAC downregulated TGFbeta signaling.
Numerous clinical reports described antioxidant and antifibrotic effects of NAC in patients with pulmonary diseases. At 600 mg t.i.d. for 5 days NAC increased glutathione levels in bronchoalveolar lavage fluid of patients with IPF. This increase was, however, not consistently seen in normal individuals or in patients with chronic obstructive lung disease (COPD). In a pilot clinical study in patients with IPF (Tomioka et al, 2005) NAC (352 mg per day, administered by inhalation for 12 months) had no effect on pulmonary function, or quality of life, but slightly reduced exercise desaturation, improved ground-glass score in HRCT and decreased mucin-like glycoprotein (KL-6) serum levels. The authors of this study concluded that NAC may delay disease progression. The interest in NAC was revived by the report by Demedts et al. (2005)who treated IPF patients with NAC, 600 mg t.i.d., p.o. for one year in addition to prednisone and azathioprine (“standard therapy”) and found that vital capacity and diffusing capacity for carbon monoxide were better preserved in patients receiving NAC than in those receiving “standard therapy” alone.
Further clinical studies with NAC alone or in combination with prednisolone and azothioprine in
patients with IPF are currently in progress. The use of NAC in IPF is not yet approved by Food and Drug Administartion (FDA) and it is doubtful that any manufacturer will apply to FDA for approval of NAC for this indication. The use of NAC is not protected by patents. It is a simple and cheap chemical. Fortunately for patients, NAC is freely available in healthfood stores as a dietary supplement.

Demedts, M., Behr, J., Buhl, R., Costabel, U., Dekhuijzen, R., Jansen,H.M., MacNee, W., Thomeer, M., Wallaert, B., Laurent, E. et al. (2005). High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 353:2229-2242.

Tomioka, H., Kuwata, Y., Imanaka, K., Hashimoto,K., Ohnishi, H., Tada, K., Sakamoto, H., and Iwasaki, H. (2005). A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology 10:449-455.

Idiopathic pulmonary fibrosis (IPF)

Why am I still alive?

I am a retired MD pharmacologist, but also a patient diagnosed 8 years ago with idiopathic pulmonary fibrosis (IPF).
According to medical literature the average life expectancy of patients with IPF is only 2 to 3 years after diagnosis. Surprisingly, I am still alive and learning how to deal with my disease.
My experience could be of interest to other patients with IPF.
There are many possible reasons for my longer survival:
1) IPF is probably not a single disease. A slowly developing form of the disease has been described. This "form" may actually be a different disease with a different cause and a better prognosis. I may be fortunate to have this "form".
2) My pulmonologist did not believe in the value of so-called standard therapy: steroids and immunosuppressants. He treated me conservatively: he did not prescribe any drugs, since it is conceivable that immunosuppressants actually shorten the survival time of some patients with IPF.
3) I decided to treat myself with N-acetyl cysteine (NAC, 600 mg, b.i.d.), vitamin C (1g q.d.) and resveratrol (50 mg q.d). A rather simple chemical, NAC has been described in scientific literature to antagonize profibrotic cytokines and experimental fibrosis in rodents. It is also an antioxidant, like vitamin C and resveratrol. NAC has been widely used in patients as a mucolytic and an antidote for acetoaminophen poisoning. It does no appear to have any side effects and is freely availablee in health food store as a dietary supplement.
4) My diagnosis was wrong. It is highly important to exclude all possible treatable causes of pulmonary fibrosis before making IPF diagnosis. Hypersensitivity to gluten, deep venous thrombosis (DVT), exposure to radon, chronic hypersensitivity alveolitis, or allergy to molds should be excluded. Patients with IPF- like symptoms should also try to change the environment
before accepting this terminal diagnosis.
Alexander Scriabine, M.D.