Cysteine is a sulfur-containing, water-soluble amino acid that is found in many proteins. Cysteine is considered a non-essential amino acid because it is formed from methionine in the body. Cysteine is very unstable and is readily oxidized to the amino acid cystine. Cystine contains two cysteines linked with a disulfide bond. It is thought that both amino acids probably undergo similar reactions in the body. Cysteine may be metabolized by several routes to yield pyruvate, taurine, or sulfide and sulfate. Insulin, CoA, glutathione (GSH), and vasopressin are other important sulfur-containing compounds derived from cysteine and cystine.

Cysteine plays an important role in liver detoxification conjugation reactions. Chemical toxins, such as bromobenzene, chlorobenzene, iodobenzene, naphthalene, benzyl chloride, are converted to mercapturic acids by conjugation with cysteine and acetylation.

The cysteine derivative N-acetyl-L-cysteine (NAC) helps prevent cellular oxidative damage in two ways: first, as an antioxidant capable of scavenging non-peroxyl radicals and, secondly, as a substrate for GSH synthesis. NAC has been used for a number of therapeutic purposes including treating respiratory diseases, acetaminophen poisoning, angina pectoris, and glutathione/antioxidant replenishment in HIV/AIDS. Newer research suggests an additional benefit in helping prevent cardiovascular disease and treating ocular symptoms in Sjogren's syndrome.

There is some controversy over the bioavailability of NAC, and its effectiveness at enhancing endogenous GSH levels. Some experts believe that cysteine is as effective as NAC, and it is less costly.

• wheat germ
• granola
• oat flakes
• ricotta
• cottage cheese
• yogurt
• pork, sausage meat
• chicken, turkey, duck
• luncheon meat

L-Cysteine, N-Acetylcysteine

• NAC aerosol spray (pharmaceutical)
• NAC liquid solution (pharmaceutical)
• L-Cysteine powder
• Cysteine/NAC tablets/capsules: (500, 600, and 1,000 mg)

Sjogren's syndrome: Preliminary research indicates that N-acetylcysteine may have a therapeutic benefit on ocular symptoms, such as ocular soreness and irritability, associated with Sjogren's syndrome.

Respiratory diseases: Pulmonary dysfunction that occurs in adult respiratory distress syndrome (ARDS) is thought to be the result of neutrophil-mediated oxidant injury. Inflammatory metabolites of membrane phospholipids (leukotrienes, thromboxanes, prostacyclin, and PAF) may also cause oxidant injury in ARDS. NAC, as a substrate for glutathione synthesis, may reduce the oxidative damage and acute lung injury that occurs in ARDS.

Oral and aerosol NAC treatment may improve some of the symptoms associated with chronic bronchitis.

Cardiovascular Disease: NAC may potentiate the vasodilatory effects of nitroglycerin (NTG) in patients with unstable angina pectoris. NAC, administered orally or intravenously with nitroglycerin, has been shown to significantly reduce the incidence of acute myocardial infarctions in patients with angina pectoris. Intravenous administration of NAC has been shown to reduce infarct size and preserve left ventricular function after acute myocardial infarction.

Elevated plasma homocysteine levels are associated with increased risk of CHD. NAC may reduce homocysteine levels in hyperhomocysteinaemic conditions by forming mixed, low molecular weight, NAC-homocysteine disulfides with enhanced renal clearance.

NAC, administered orally, has also been shown to cause a dose-related increase in HDL-cholesterol levels without altering TC, TG, or lipoprotein (a) levels. A 16.2% increase in HDL cholesterol was seen at the highest dose (3,600 mg per day).

HIV: HIV patients have been shown to have a compromised antioxidant defense system and decreased intracellular GSH levels in their circulating T cells. NAC has been proposed as a treatment to replenish depleted GSH and inhibit reactive oxygen intermediates in HIV. However, the ability of NAC to increase GSH levels in white blood cells of AIDS patients is still controversial.

Acetaminophen poisoning: NAC is commonly used in the treatment of acetaminophen (paracetamol) overdosage. NAC (oral and intravenous) mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. NAC may also help combat the enhanced acetaminophen toxicity that is associated with alcohol ingestion.

Corneal damage: Glutathione is found in high concentrations in the cornea and lens of the eye, where it probably functions as an antioxidant, protecting the eyes against cataracts. Animal studies indicate that NAC may help reduce cigarette smoke-induced oxidative damage to corneal cells, possibly by enhancing GSH levels.

• Acetaminophen poisoning: The typical oral dosage of NAC is 140 mg/kg body weight, followed four hours later by 70 mg/kg every four hours for an additional 17 doses. Oral treatment must be started within eight hours of an acetaminophen overdose to prevent hepatoxicity. Oral NAC is typically administered for 72 hours; intravenous NAC for 20 to 52 hours. It is recommended to give the intravenous loading dose over 60 minutes, instead of 15 minutes, to reduce the risk of adverse reactions.
• Bronchial disease: 200 mg bid
• HDL cholesterol: 1,200 to 3,600 mg per day
• Antioxidant protection/general health: 500 mg/day to start. Individuals may increase the dose to 3 to 4 g/day as tolerated.

Taking high doses (over 7 g) of cysteine may be harmful and should be avoided.

Oral NAC treatment may cause nausea, vomiting, and diarrhea.

NAC infusion in acetaminophen poisoning may cause anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress.

Intravenous nitroglycerin combined with intravenous NAC may cause symptomatic hypotension.

Fatalities have occurred from intravenous overdosage of NAC.

Oral NAC treatment, for acetaminophen poisoning, is contraindicated in the presence of coma or vomiting or if activated charcoal has been given by mouth.

Individuals with cystinuria should avoid, or limit, their intake of cysteine supplements.

D-cysteine, D-cystine and 5-methyl cysteine are toxic forms that should not be used.

N-Acetylcysteine (NAC) may potentiate the antihypertensive effect of ACE inhibitors via a nitric oxide-dependent mechanism (Suárez et al. 1995). NAC (1200 mg/day) potentiated the reduction in systolic and diastolic blood pressure induced by lisinopril (10 to 30 mg/day) in six patients with essential hypertension. In spontaneously hypertensive rats, NAC (300 mg/kg IV) potentiated the blood-pressure lowering effects of captopril and enalaprilat (Ruiz et al. 1994).

Treatment with NAC infusions (4 to 10 d/day) combined with prednisone (1 mg/kg) reversed cholestatic jaundice and pure red cell aplasia in a patient receiving gold sodium thiomalate (160 mg IM) for progressive psoriatic arthritis (Hansen et al. 1991). It is not known if these effects were attributable to NAC combined with prednisone or NAC therapy alone.

Adjunctive treatment with high dose NAC (600 mg po tid) in patients on maintenance immunosuppressive therapy for fibrosing alveolitis positively affected clinical course and pulmonary function (Behr et al. 1997). These findings may warrant further investigation in controlled clinical trials.

In one in vitro study, NAC (1 mM) significantly inhibited cisplatin-induced reactive oxygen species, an indicator of cytotoxicity, in bladder cancer cells (Miyajima et al. 1999). The reduction was attributed to the ability of NAC to enhance glutathione levels.

In vitro and in vivo studies have established that NAC protects against doxorubicin-induced cardiotoxicity (D'Agostini et al. 1998; Doroshow et al. 1981). NAC interacted synergistically with doxorubicin to prevent tumorigenicity, metastasis, and alopecia in mice (D'Agostini et al. 1998). In addition, NAC, alone and in combination with doxorubicin, enhanced survival in mice injected with melanoma cells (D'Agostini et al. 1998; De Flora et al. 1996). Clinical trials are needed to confirm these effects in humans.

In vitro, NAC potentiated the antiplatelet effects of nitroglycerin (Chirkov and Horowitz 1996).

Clinically, the combination of NAC (bolus dose of 2 g) and nitroglycerin (1.5 µg/kg/min) prolonged vasodilation and minimized the development of tolerance in patients with angina pectoris and normal left ventricular function (Pizzulli, et al. 1997). Positive results were also obtained in a double blind, placebo-controlled study of 200 patients with unstable angina taking transdermal nitroglycerin either alone or in combination with NAC; the combination of NAC and nitroglycerin resulted in fewer deaths and myocardial infarctions (Ardissino et al. 1997). In another randomized, double blind, placebo-controlled study, NAC (2400 mg bid) potentiated the effects of isosorbide-5-mononitrate (60 mg po) and increased exercise capacity in 10 patients with angina pectoris, both without nitrate tolerance (Svendsen et al. 1989). Although NAC may prevent nitrate tolerance, the high incidence of side effects, particularly intolerable headache, may preclude its clinical use (Ardissino et al. 1997; Iversen 1992).

In one study, topical application of NAC (15% w/v lotion) and oxiconazole prolonged the mean residence time of oxiconazole in the upper nail layers (51 to 100 mm) by as much as 73% (van Hoogdalem et al. 1997). NAC may increase binding of oxiconazole to nails.

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