Supplement Spotlight: N-acetyl Cysteine

Introduction

N-acetyl cysteine (NAC) is the acetate derivative of the nonessential sulfur-containing amino acid cysteine. In an inhaled form, NAC is a prescription drug used for acute and chronic obstructive or inflammatory lung disorders including bronchitis, pneumonia, influenza, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. Inhaled NAC thins mucus in the lungs, and normalizes its production so that mucus doesn't block the airway. Oral NAC is also very useful, and doesn't require a prescription.

Once you already have life-threatening respiratory distress, oral NAC isn't effective. However, oral NAC is very effectibe at preventing or lessening the severity of respiratory conditions and lung injury if supplements are taken prior to exposure to pathogens/toxins.

We'll review some specific examples later. First, we need to understand how NAC protects us.

NAC Builds Glutathione

L-cysteine has an important role as a building block of glutathione. Glutathione (gamma-glutamylcysteinylglycine) is a tripeptide that participates in a variety of detoxification, transport, and metabolic processes. Glutathione is the most abundant antioxidant within our cells. The balance between its reduced form (often abbreviated GSH) and oxidized form glutathione disulfide (GSSG) maintains the sulfur-hydrogen groups of intercellular proteins in the correct oxidation states for optimum metabolic functions. GSH is also substrate for peroxidase reactions, which destroy reactive peroxide radicals, and is involved in leukotrienes synthesis.

Reactive oxygen metabolites and leukotrienes are the main players in the biochemistry of airway inflammation. They directly cause symptoms of asthma, allergies, and breathing difficulties associated with inhaled toxins.

Leukotrienes

Arachidonic acid is a polyunsaturated fat always present in cell membranes. Inflammatory triggers (i.e. pathogens, allergens) signal enzymes to turn arachidonic acid into a series of very troublesome leukotrienes. This leukotriene series acts to keep inflammatory conditions running once they're initiated. They're also stimulators of bronchial constriction, and increase production of lung mucus. You only need to produce a tiny amount to narrow the breathing passages and precipitate an asthma attack.

Reactive Oxygen Metabolites

Abnormally high levels of leukotrienes and reactive oxygen metabolites (ROM) are responsible for chronic bronchial and lung inflammation. Most ROM are naturally produced by activated immune cells, increased metabolism, and strenous exercise, as well as in response to tissue injury. They are part of our defense and repair mechanisms, but they're also capable of irritating and inflaming tissues all over the body. Prolonged or chronically high ROM levels are not beneficial - ROM begin to damage instead of repairing tissues.

Excessive levels of ROM are also caused by external agents including tobacco smoke, toxic chemicals, and mining or agricultural dust.

Antioxidants to the Rescue

Antioxidants reduce the frequency and severity of asthma attacks. They combat the exacerbation of lung disorders induced by inhalation of pollutants and irritants, and lessen respiratory distress and permanent lung injury caused by inhaling damaging substances. Asthmatics tend to have reduced blood levels of antioxidants, especially vitamins A, C and E, and selenium. Severe, persistent asthma is associated with below-RDA intakes of magnesium and antioxidants. Antioxidants play crucial roles in respiratory immunity. In children and the elderly, antioxidant supplementation has been shown to reduce respiratory infection incidence.

Vitamin C is the primary antioxidant in the lungs, and is a powerful antihistamine. It enhances immunity and reduces the severity of allergic responses. Glutathione is second in importance after vitamin C and they're synergistic. Working together, glutathione and C normalize leukotriene activity and proliferation, helping to prevent "runaway" inflammation. Lung function and immune response are severely compromised if these antioxidants are below optimal levels. The benefits of supplementing NAC orally prior to the development of lung disorders cannot be overemphasized:

  • NAC is one of only a few supplements proven to help control chronic obstructive pulmonary disease (doses 400-1,200 mg/day).
  • Mustard gas inhalation causes lung tissue injury, resulting in respiratory distress syndrome. Guinea pigs inhaling 2-chloroethyl ethyl sulfide (mustard gas analouge) had severe lung injury in one hour. Lung edema, congestion, hemorrhaging, and inflammation increased progressively over the following 21days. A single dose of NAC (0.5 g) fed just before 2-chlorethyl ethyl sulfide exposure was ineffective at counteracting these effects. However, guinea pigs given NAC in drinking water for three or 30 days (two groups) prior to exposure had a 69-76 percent reduction in lung injury.
  • ROM are formed in response to influenza infection, and increase the pathogenicity of the virus. Mice were infected with influenza, then given NAC (1 g/kg/day) or nothing. They all developed disease symptoms, and many died, but a higher percentage of the NAC group recovered. NAC increased synthesis of glutathione, which probaly counteracted the ROM effects.
  • Oxidative stress is involved in asthma and chronic inhalant allergies. Allergically sensitized rats were given NAC (3 mmol/kg/day) for one week, then were exposed to allergens. Nac didn't affect the immediate bronchial spasm reaction to allergen exposure. This later hyperactivity is largely stimulated by leukotrienes and ROM - which are reduced in activity by glutathione.
  • Rats were exposed to the smoke of cigarettes/hour/day for four weeks and fed a low protein diet. Liver and lung glutathione levels were reduced from both diet and smoke, and ROM levels were increased. However, there was no reduction in lung glutathione when the diet was supplemented with NAC.
  • Oxidants are implicated in lung inflammation caused by air pollution. Rats were exposed to aerosol dust for five hours. One group was given 50 mg/kg NAC one hour prior to exposure. Rats breathing aerosol dust showed significant oxidative stress and slight lung edema, but NAC-treatment prevented these alterations.

NAC and Glutathione Strengthen Immunity

Diets low in produce result in vitamin C deficiencies, while diets low in animal protein result in sulfur amino acid deficiencies. Stress, strenous excercise, and chronic wasting disease such as malaria, tuberculosis, and AIDS also reduce respiratory immunity. Many people with AIDS eventually die of pneumonia or tuberculosis because their respiratory immunity is so compromised. More HIV-positive Africans die from tuberculosis than from actual AIDS. To complicate matters further, environmental and pathogenic toxins become more virulent when gluathione and other sulfur proteins are powerful detoxifiers.

Besides its antioxidant action and effects on respiratory immunity, glutathione has an important function in generalized immune reactivity by modulating T-cell natural killer activity. Regular NAC supplementation can benefit elderly, malnourished, chronically ill, and immune-suppressed persons. Several studies have shown that HIV-positive patients in different stages of infection have abnormally low cysteine and glutathione levels. The constant stress of fighting an infection that suppresses general immunity requires high levels of glutathione activity. Since reduced food intake and muscle wasting are associated with HIV, cysteine/glutathione deficiency can occur rapidly in AIDS patients, resulting in a rapid decline in health.

Based on word of mouth, NAC supplementation in the range 1-5 g/day is fairly popular among HIV-positive individuals. Some controlled research studies report improved lymphocyte counts, T-cell, and natural killer cell functions, and reduced HIV viral levels in AIDS patients. The improvements occurred regardless of wheather the patients were taking antiretroviral drugs simultaneously. Effective doses were 0.8-3.2 g/day: combined NAC and vitamin C supplementation was even more beneficial. A recent study in which 30 Brazilian patients were given only 600 mg/day in conjunction with drug treatment failed to show improvement over placebo after 180 days.

No matter the outcome in a complicated disease like AIDS, the vaule of supplemental NAC is clearly established. A good rule of thumb for treating respiratory conditions such as asthma is 300-500 mg NAC three times daily. Persons with immune suppression may need to double this dosage.

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