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Cysteine/cystine

Also known as: cysteine, cystine, L-Cystine, N-Acetylcysteine, NAC, L-Cysteine

Overview

L-Cysteine is a sulfur-containing non-essential amino acid crucial for various biological functions. It is found in dietary proteins like poultry, eggs, dairy, and legumes. L-Cystine is its oxidized dimer form, linked by a disulfide bond. N-Acetylcysteine (NAC) is a synthetic derivative of L-cysteine, widely used as a supplement and drug due to its enhanced bioavailability. Cysteine and its derivatives are primarily supplemented for their role in antioxidant support, particularly as a precursor to glutathione, a major intracellular antioxidant. They also play a role in detoxification processes, respiratory health, and have shown potential in augmenting treatments for certain psychiatric disorders. Cysteine and cystine are also vital in parenteral nutrition, especially for neonates, to ensure proper amino acid profiles and support growth. The research on cysteine and its derivatives, particularly NAC, is extensive, with a moderate to high level of maturity, including numerous randomized controlled trials and systematic reviews.

Benefits

Cysteine and its derivatives offer several evidence-based benefits. A primary effect is the significant increase in plasma cysteine levels, particularly observed in neonates receiving parenteral nutrition, with a mean difference of approximately 2.48 micromoles/100 ml (95% CI 1.44–3.53). This is crucial for improving plasma amino acid profiles and growth parameters in preterm infants. Cysteine is also rate-limiting for glutathione synthesis, thereby enhancing cellular antioxidant capacity and supporting detoxification pathways. N-Acetylcysteine (NAC) has shown strong efficacy as an augmentation strategy for selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD), with meta-analyses of RCTs demonstrating significant symptom improvement. While the exact effect sizes vary, the clinical significance is notable, with benefits typically observed over weeks to months. Additionally, NAC exhibits expectorant effects, benefiting respiratory conditions. Some research in model organisms suggests potential lifespan extension, though its relevance to humans is currently unclear.

How it works

Cysteine's primary mechanism of action revolves around its role as a precursor for glutathione (GSH) synthesis. GSH is a critical intracellular antioxidant that helps protect cells from oxidative damage. NAC, being an acetylated derivative, provides cysteine in a highly bioavailable form, effectively replenishing intracellular GSH stores and modulating oxidative stress. By enhancing GSH levels, cysteine and NAC contribute to maintaining cellular redox balance and supporting the body's detoxification pathways. In the context of psychiatric disorders, particularly with NAC, it is believed to modulate neurotransmitter systems, such as glutamatergic pathways, indirectly through its redox-modulating effects. NAC is well absorbed orally and converted to cysteine, while cysteine itself is less stable and can oxidize to cystine, which is then absorbed and reduced intracellularly to cysteine.

Side effects

Cysteine and its derivatives, including NAC, are generally considered safe when taken within recommended dosages. The most common side effects, especially at higher doses, are gastrointestinal symptoms such as nausea, vomiting, and diarrhea, reported in over 5% of users. Uncommon side effects (1-5% incidence) include allergic reactions, skin rash, and headaches. Rare side effects (less than 1%) can include anaphylactoid reactions, primarily associated with intravenous NAC administration, and other rare hypersensitivity reactions. Caution is advised when combining cysteine or NAC with other expectorants or drugs that affect glutathione metabolism. There is also a potential interaction with nitroglycerin and certain chemotherapeutics. Contraindications include known hypersensitivity to cysteine or NAC. It is generally not recommended for children under 2 years of age without medical supervision. Pregnant and breastfeeding women should consult a healthcare provider before use. Neonates receiving cysteine in parenteral nutrition require careful dosing and close medical monitoring.

Dosage

The minimum effective dose of cysteine and its derivatives varies depending on the specific indication. For N-Acetylcysteine (NAC) in adults, common and effective doses range from 600 mg to 1200 mg per day. For cysteine/cystine used in parenteral nutrition, particularly for neonates, dosages are precisely adjusted according to clinical protocols and individual patient needs. The maximum safe dose for adults is generally considered to be up to 1200 mg/day for NAC or 900 mg/day for cysteine/cystine without harmful effects. Consistent daily dosing is important for optimal benefits, and in conditions like psychiatric disorders, clinical improvements may take several weeks to months to become apparent. NAC is the preferred form for oral supplementation due to its superior stability and bioavailability compared to L-cysteine. Adequate intake of other amino acids and nutrients, such as tyrosine and sufficient calories, can be important cofactors for the optimal utilization of cysteine.

FAQs

Is cysteine supplementation safe?

Yes, cysteine and its derivatives are generally safe within recommended doses. Gastrointestinal discomfort like nausea or diarrhea is the most common side effect, especially at higher intakes. Avoid excessive doses.

Can cysteine help with mental health?

N-Acetylcysteine (NAC), a cysteine derivative, has shown evidence as an effective adjunctive treatment for obsessive-compulsive disorder (OCD) and other psychiatric conditions, improving symptoms when used with standard therapies.

How quickly does cysteine work?

Plasma cysteine levels can increase within days of supplementation. However, clinical benefits, particularly for psychiatric conditions, typically require consistent use over several weeks to months to become noticeable.

Is NAC better than cysteine?

For oral supplementation, NAC is generally preferred over L-cysteine because it is more stable and has better oral bioavailability, meaning more of it is absorbed and utilized by the body.

Can children take cysteine supplements?

Cysteine supplements are generally not recommended for children under 2 years of age. For older children, medical supervision is advised due to specific dosing requirements and safety considerations.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC8855743/ – This systematic review by Soghier et al. (2006) analyzed randomized controlled trials on cysteine/cystine supplementation in parenteral nutrition for preterm infants. It found significant increases in plasma free cyst(e)ine levels and improved outcomes, supporting the use of cysteine in this vulnerable population despite some heterogeneity in studies.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6017824/ – Plaza et al. (2018) conducted a review of clinical trials on L-Cysteine, identifying its broad potential for antioxidant, detoxification, and health-promoting effects. The review highlighted the diverse applications of L-cysteine but also noted variability in study quality and outcomes across the 1638 analyzed trials.
https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1421150/full – Eghdami et al. (2024) performed a systematic review and meta-analysis on NAC augmentation for OCD. Their findings indicated that NAC is a promising adjunct therapy, significantly improving symptoms with an acceptable safety profile, though they recommended further large-scale randomized controlled trials.
https://www.rivm.nl/bibliotheek/rapporten/2024-0086.pdf – The RIVM Risk Assessment Report (2024) provided a safety evaluation of NAC, L-cysteine, and L-cystine supplements. It concluded that maximum safe adult doses are 1200 mg/day for NAC and 900 mg/day for cysteine/cystine, while also cautioning against use in children under 2 years due to potential gastrointestinal side effects at higher doses.
https://onlinelibrary.wiley.com/doi/10.1111/acel.14392 – Wiley et al. (2024) conducted a meta-analysis on the impact of cysteine supplementation on lifespan in model organisms (mice, nematodes, fruit flies). While some lifespan extension effects were observed, the study noted limitations due to species differences and experimental heterogeneity, making human relevance uncertain.