NAC Clinical Evidence

NAC and Oxidative Status

Urology
Ciftci H, et al. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. 2009 Jul;74(1):73-6. 

Topic: 
Can N-acetylcysteine (NAC) improve oxidative/antioxidant status and semen parameters in infertile men?

Background:

Free radicals can harm sperm, and may play a role in male infertility. Can NAC, an antioxidant, improve the antioxidant status of infertile men?

Study Type:

Human clinical intervention trial

Study Design:

Placebo-controlled. Subjects took NAC or placebo. Blood and sperm samples were taken to asses the subjects’ oxidative status and sperm parameters.

Subjects:

120 infertile adult men

Dosage:

600 mg/day for 3 months or placebo

Results:

After treatment, the total antioxidant capacity was greater and the oxidative stress index was lower in men who had taken NAC. In addition, their semen quality improved.

Conclusion:

“We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility.” 

NAC and Oxidative Status

Physiological Research 
Zembron-Lacny A, et al. The comparison of antioxidant and hematological properties of N-acetylcysteine and alpha-lipoic acid in physically active males. 2009;58(6):855-61. 

Topic: 
How do the antioxidants N-acetylcysteine (NAC) and alpha-lipoic acid (ALA) affect antioxidant status and blood parameters in physically active males?

Background:

Previous research has shown than both NAC and ALA increase antioxidant activity. Does this antioxidant effect cause any change in blood parameters such as levels of red blood cells and hemoglobin?

Study Type:

Human clinical observation trial

Study Design:

Placebo-controlled. Subjects took NAC, ALA or a placebo. Blood samples were taken and analyzed.

Subjects:

28 healthy men

Results:

1,200 mg for 8 days, in 2 daily doses 

Both NAC and ALA increased antioxidant activity and reduced protein carbonylation and lipid peroxidation (markers of oxidative stress and cell damage) by more than 30%. However, NAC also:

  • Increased levels of glutathione (an antioxidant produced by the body) by 33%
  • Increased levels of erythropoietin (which stimulates the production of red blood cells) by 26%
  • Increased levels of hemoglobin (the iron-containing protein in blood) by 9%
  • Increased levels of hematocrit (the percentage of blood occupied by red blood cells) by 9%
  • Increased average red blood cell volume and average mass of hemoglobin per red blood cell by 12%.

Conclusion:

“Our study has shown that both N-acetylcysteine and alpha-lipoic acid intake reveal an antioxidant action, but only N-acetylcysteine improves the haematological response.” 

NAC and Detoxification

Pharmacology 
Ventura P, et al. Urinary and plasma homocysteine and cysteine levels during prolonged oral N-Acetylcysteine therapy. 2003 Jun;68(2):105-14. 

Topic: 
How does supplementation with NAC affect levels of homocysteine and cysteine in blood and urine?

Background:

Homocysteine is a toxin associated with cardiovascular disease. Cysteine is an amino acid found in high-protein foods as well as some grains and vegetables.

Study Type:

Human clinical intervention trial

Study Design:

Subjects took NAC or no therapy, and had their levels of homocysteine and cysteine monitored.

Subjects:

51 healthy subjects

Dosage:

No therapy or 600 mg/day or 1,800 mg/day for 2 months, followed by a 1-month washout period and another 2 months of 1,800 mg/day for all groups.

Results:

Those who took NAC saw a significant, dose-dependent decrease in their plasma levels of homocysteine and a small increase in cysteine levels. These results indicate that NAC is an effective detoxifier of homocysteine.

Conclusion:

“This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor response to vitamins.” 

NAC and Immune Function

European Respiratory Journal 
De Flora S, Grassi C and Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. 1997;10:1535–41. 

Topic: 
Can supplementation with NAC prevent and/or treat influenza-like infections?

Background:

NAC, a precursor of glutathione, has been used to prevent and treat respiratory diseases and diseases involving oxidative stress. Can it help prevent or treat flu-like illnesses?

Study Type:

Human clinical intervention trial

Study Design:

Multi-center, randomized, double-blind, placebo-controlled. Subjects took NAC or a placebo and were monitored for flu-like illnesses.

Subjects:

262 men and women without chronic respiratory disease

Dosage:

600 mg, twice daily for 6 months

Results:

Subjects treated with NAC had significantly fewer incidences of flu-like illness. Their periods of illness were also shorter and less severe. Interestingly, they contracted the A/H1N1 virus with a frequency similar to that of the control group, but of those who tested positive for the virus, 75% of the treatment group was asymptomatic, while only 21% of the placebo group was.

Conclusion:

“Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.” 

NAC and Immune Function

Clinical Chemistry and Laboratory Medicine 
Spada C, et al. The effect of N-acetylcysteine supplementation on viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment. 2002 May;40(5):452-5. 

Topic: 
Is NAC a useful adjunct therapy for HIV patients undergoing antiretroviral treatment?

Background:

In the normal progression of HIV, patients typically see their levels of CD4 cells (T cells that help the immune system respond to viruses) fall, while their viral loads increase and their blood parameters worsen. Can NAC work together with antiretroviral treatment to halt these changes?

Study Type:

Human clinical intervention trial

Study Design:

Double-blind, placebo-controlled. Subjects took NAC or a placebo. At 60, 120 and 180 days, their viral load, levels of CD4 and CD8 cells (T cells that destroy infected cells), lymphocyte (a kind of white blood cell) counts and hematocrit (the percentage of whole blood that consists of red blood cells) were measured.

Subjects:

20 subjects with HIV undergoing antiretroviral treatment

Dosage:

600 mg/day for 180 days

Results:

Subjects in the treatment group had an increase in CD4 levels that took place earlier than in the control group. The treatment group also maintained stable hematocrit levels. 

NAC and Immune Function

Free Radical Biology and Medicine 
Arranz L, et al. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. 2008 Nov 1;45(9):1252-62. 

Topic: 
Can supplementation with NAC improve oxidative parameters in postmenopausal women?

Background:

As people age, oxidative stress takes a toll on leukocyte (white blood cell) function. Can NAC slow this decline?

Study Type:

Human clinical intervention trial

Study Design:

Subjects took NAC, and researchers then measured markers of the functioning of different kinds of white blood cells, such as lymphocytes and neutrophils, at 2 and 4 months. They also measured levels of cytokines, a signaling protein used by immune cells. A younger group of women was used as a control group. Measurements were repeated 3 months after supplementation had ended.

Subjects:

36 healthy postmenopausal women, aged 50 and older, plus a control group of 18 healthy women aged 30-49

Dosage:

600 mg, for 4 months

Results:

Before treatment, the older women showed greater impairment of immune function and greater evidence of oxidative stress than the younger women. However, after treatment, the older women’s parameters had significantly improved, coming closer to those of the younger women. These effects persisted 3 months after supplementation had ended.

Conclusion:

“The present findings suggest that a short period of NAC supply (i.e., 2-4 months) at the dose used may lead to prolonged strengthening of immune defence in postmenopausal women, likely by increasing the leukocyte glutathione pool. Thus, NAC could contribute to maintenance of good health and quality of life in postmenopausal women by decreasing the probability of immune system-related diseases, such as infections, in aging.” 


NAC Mechanism of Action

Like vitamin C, NAC also has antioxidant and detoxification powers.

  • Antioxidant: NAC enhances blood antioxidant levels, specifically levels of glutathione, by releasing cysteine, a precursor in the production of glutathione.
  • Immune-modulation: There is a direct correlation between glutathione levels and immune function.
  • Detoxification: NAC lowers levels of the toxin homocysteine by forming disulfide complexes with it, allowing it to be excreted from the body. NAC has also been found to reduce levels of chromate, borate, mercury and arsenic in animals by increasing excretion of these harmful substances. It combines with mercury-containing compounds to help remove them from the body.