N-acetyl cysteine as a therapeutic supplement

• DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.
• PRINCIPAL PROPOSED USES: Angina pectoris (in combination with conventional treatment), chronic bronchitis, preventing influenza
• OTHER PROPOSED USES: Antioxidant, Anti-inflammatory, Chemical dependency (cocaine), chemotherapy support, chronic blepharitis, colon cancer prevention, female infertility caused by polycystic ovary syndrome, human immunodeficiency virus support, liver failure, pathological gambling (gambling addiction), protection against kidney damage caused by contrast agents, schizophrenia, Sjögren’s syndrome

Overview

N-acetyl cysteine (NAC) is a specially modified form of the dietary amino acid cysteine. When taken orally, NAC is thought to help the body make the important antioxidant enzyme glutathione. It has shown promise for a number of conditions, especially chronic bronchitis.

Requirements and Sources

There is no daily requirement for NAC, and it is not found in food.

Therapeutic Dosages

Optimal levels of NAC have not been determined. The amount used in studies has varied from 250 to 1,500 milligrams (mg) daily.

It has been suggested that NAC may increase the excretion of trace minerals; some evidence, however, suggests that this effect is too minimal to make a real difference. Prudence suggests that individuals taking NAC for an extended period of time should also consider taking a standard multivitamin/mineral supplement.

Therapeutic Uses

Significant but not entirely consistent evidence suggests that regular use of NAC is helpful for individuals with chronic bronchitis (a condition commonly associated with smoking and emphysema) in reducing the frequency of acute flare-ups of the condition. Regular use of NAC may help prevent influenza, possibly by stimulating immunity.

One substantial study found evidence that NAC may augment the effectiveness of clomiphene, a drug used for female infertility, in women with polycystic ovary syndrome. Another study found NAC far less effective for this purpose than the drug metformin; however, it still could have provided some benefit.

Mixed evidence suggests that NAC may also enhance the effectiveness of the drug nitroglycerin, used for the treatment of angina. However, severe headaches can develop as a side effect. NAC may be helpful in a life-threatening condition called acute respiratory distress syndrome. Very high dosages of NAC are used in hospitals as a conventional treatment for acetaminophen poisoning. One should not attempt to self-treat angina, acute respiratory distress syndrome, or acetaminophen poisoning. Medical supervision is absolutely essential because of the very real risk of death in these conditions. According to some, but not all, studies, NAC may be helpful for preventing complications that occur during cardiac surgery.

Some research has also suggested that NAC may be helpful for Sjögren’s syndrome (a disease that causes dry eyes, among other symptoms), chronic blepharitis (ongoing infections of the eyelid), severe liver disease, and reducing the side effects of the cancer chemotherapy drug ifosfamide. Other evidence hints that NAC might help offset the carcinogenic effects of smoking and reduce colon cancer risk. Weak evidence hints that NAC might reduce some side effects (specifically, cardiac toxicity and hair loss) caused by the cancer chemotherapy drug doxorubicin.

NAC has been proposed as supportive therapy for Human Immunodeficiency Virus (HIV). Despite some intriguing results, the evidence is inconsistent at best. Several studies have suggested that NAC may be beneficial as an aid to treating various mental health disorders, including schizophrenia, cocaine dependence, and even pathological gambling.

To get more information from certain types of X-rays, radiologists often administer substances called contrast agents. However, contrast agents can damage the kidney. It has been suggested that NAC can help protect the kidney from such damage; however, the most recent and best-designed study failed to find any benefit.

One double-blind trial failed to find NAC helpful for head and neck or lung cancer. Studies have also failed to find NAC helpful for treating viral hepatitis, preeclampsia, or enhancing sports performance.

Scientific Evidence

Chronic bronchitis. Individuals who have smoked cigarettes for many years eventually develop deterioration in their lungs, leading to various symptoms, including chronic production of thick mucus. This so-called chronic bronchitis (closely related to chronic obstructive pulmonary disease) tends to flare up periodically into severe acute attacks, possibly requiring hospitalization.

Regular use of NAC may diminish the number of these attacks. A review and meta-analysis selected eight double-blind, placebo-controlled trials of NAC for chronic bronchitis. The results of these studies, involving a total of about 1,400 individuals, suggest that NAC taken daily at a dose of 400 to 1,200 mg can reduce the number of acute attacks of severe bronchitis. However, the largest and best of these studies, a three-year double-blind, placebo-controlled trial of 523 people, failed to find that use of NAC at a dose of 600 mg daily reduced exacerbations or delayed the typical progressive worsening of lung function. It is not clear how NAC works (if it does); the old concept that it acts by thinning mucus may not be correct.

Influenza. In a double-blind, placebo-controlled study of 262 seniors, regular use of NAC at a dose of 600 mg twice daily helped prevent the development of influenza-like illnesses. Over the six-month study period, only 25 percent of participants taking NAC developed flulike symptoms, compared with 79 percent in the placebo group, a statistically significant difference.

Blood tests suggested that NAC did not prevent influenza infection; about as many people showed antibodies indicating influenza infection in the NAC group as in the placebo group. Rather, the supplement seemed to reduce the rate at which influenza infection became severe enough to cause noticeable symptoms. Tests of immune function hinted that NAC functioned by increasing the strength of the immune response.

Angina pectoris. Angina pectoris is a squeezing feeling in the chest caused by inadequate blood supply to the heart. It can be a precursor of heart attacks. People with angina often use the drug nitroglycerin to relieve symptoms. One four-month double-blind, placebo-controlled study of two hundred people with heart disease found that the combination of nitroglycerin and NAC significantly reduced the incidence of heart attacks and other severe heart problems. NAC alone and nitroglycerin alone were not as effective. The only problem was that the combination of nitroglycerin and NAC caused severe headaches in many participants. This effect has been seen in other studies as well.

NAC may also help in cases of nitroglycerin tolerance, a condition in which the drug becomes less effective over time. In a small double-blind study of thirty-two people with angina, tolerance developed in fifteen of sixteen individuals who took nitroglycerin only but in just five of sixteen individuals who took nitroglycerin plus 2 grams of NAC daily. However, other studies have found no benefit.

Female infertility. In a double-blind, placebo-controlled study of 150 women suffering from infertility who had not responded to treatment with the fertility drug clomiphene, the use of NAC at 1,200 mg daily significantly augmented the effectiveness of clomiphene. Treatment was begun on day three of the menstrual cycle and continued for five days. About 20 percent of women in the NAC plus clomiphene group became pregnant, compared with 0 percent in the placebo plus clomiphene group.

Acute respiratory distress syndrome. A double-blind, placebo-controlled clinical trial compared the effectiveness of NAC, Procysteine (a synthetic cysteine building-block drug), and a placebo in forty-six people with acute respiratory distress syndrome. This catastrophic lung condition can occur when an unconscious person inhales a small amount of their own vomit. Both NAC and Procysteine reduced the severity of the condition in some people (compared with a placebo). However, overall, it did not reduce the number of deaths.

Colon cancer prevention. A preliminary double-blind, placebo-controlled study of NAC enrolled sixty-two individuals, each of whom had a polyp removed from the colon. The abnormal growth of polyps is closely associated with the development of colon cancer. In this study, the potential anticancer benefits of NAC treatment were evaluated by taking a biopsy of the rectum. Individuals taking NAC at 800 mg daily for twelve weeks showed more normal cells in the biopsied tissue compared with those in the placebo group.

Serious COVID-19. Researchers believe there is a potential to re-purpose NAC to use as a supportive treatment for people with serious cases of COVID-19. NAC is a molecule with two antioxidant mechanisms. It may neutralize free radicals and also restore glutathione (GSH), which is often depleted in patients who have severe COVID-19.

Safety Issues

NAC appears to be a very safe supplement when taken alone, although one study in rats suggests that sixty to one hundred times the normal dose can cause liver injury. The combination of nitroglycerin and NAC can cause severe headaches. Safety in young children, women who are pregnant or nursing, and individuals with severe liver or kidney disease has not been established.

Bibliography

Cakir, O., et al. "N-acetylcysteine Reduces Lung Reperfusion Injury After Deep Hypothermia and Total Circulatory Arrest." Journal of Cardiac Surgery, vol. 19, 2004, pp. 221-225.

Dhalla, N. S., et al. "Status of Myocardial Antioxidants in Ischemia-Reperfusion Injury." Cardiovascular Research, vol. 47, 2000, pp. 446-456.

Di Marco, F., et al. "Where Are We with the Use of N-acetylcysteine as a Preventive and Adjuvant Treatment for COVID-19?" European Review for Medical and Pharmacological Sciences, vol. 26, no. 2, 2022, pp. 715-721, doi:10.26355/eurrev‗202201‗27898. Accessed 21 Nov. 2024.

Eren, N., et al. "Effects of N-acetylcysteine on Pulmonary Function in Patients Undergoing Coronary Artery Bypass Surgery with Cardiopulmonary Bypass." Perfusion, vol. 18, 2003, pp. 345-350.

Ershad, Muhammed, et al. “N-Acetylcysteine - StatPearls.” NCBI, 29 Feb. 2024, www.ncbi.nlm.nih.gov/books/NBK537183. Accessed 21 Nov. 2024.

Fischer, U. M., et al. "Myocardial Apoptosis Prevention by Radical Scavenging in Patients Undergoing Cardiac Surgery." Journal of Thoracic and Cardiovascular Surgery, vol. 128, 2004, pp. 103-108.

Fischer, U. M., P. Tossios, and U. Mehlhorn. "Renal Protection by Radical Scavenging in Cardiac Surgery Patients." Current Medical Research and Opinion, vol. 21, 2005, pp. 1161-1164.

Larowe, S. D., et al. "Is Cocaine Desire Reduced by N-acetylcysteine?" American Journal of Psychiatry, vol. 164, 2007, pp. 1115-1117.

“N-Acetylcysteine.” Memorial Sloan Kettering Cancer Center, 21 Oct. 2022, www.mskcc.org/cancer-care/integrative-medicine/herbs/n-acetylcysteine. Accessed 21 Nov. 2024.

Tossios, P., et al. "N-acetylcysteine Prevents Reactive Oxygen Species-Mediated Myocardial Stress in Patients Undergoing Cardiac Surgery." Journal of Thoracic and Cardiovascular Surgery, vol. 126, 2003, pp. 1513-1520.