cysteine

Cysteine is a sulfur‑containing non‑essential amino acid, meaning under normal conditions the body can synthesize it from methionine via the transsulfuration pathway. Chemically, cysteine (L‑2‑amino‑3‑mercaptopropanoic acid) contains a thiol (sulfhydryl) group that imparts unique reactivity, allowing it to form disulfide bonds essential for tertiary structure in proteins. The thiol group also makes cysteine a key donor of sulfur in metabolism and a linchpin in redox homeostasis. Cysteine is a constituent of many proteins and enzymes and plays a central role in the synthesis of glutathione, one of the body’s most potent intracellular antioxidants. The ability of cysteine to form disulfides also underpins protein structural stability, particularly in extracellular proteins such as keratin in hair and nails. Cysteine's importance extends to detoxification pathways, where it contributes sulfur for conjugation reactions that neutralize toxic substances. Although the human body can produce cysteine, its synthesis can be limited by availability of methionine, making dietary sources clinically relevant, particularly in populations with increased oxidative stress, aging or restricted protein intake. Metabolic disorders in cysteine pathways, such as cystathioninuria or homocystinuria, underscore cysteine’s integration into broader amino acid metabolism, though these conditions are rare. In summary, cysteine is an amino acid with multifunctional roles in structural biology, antioxidant defenses, and cellular metabolism, bridging dietary intake and endogenous synthesis.

Cysteine serves multiple biochemical and physiological functions that are fundamental to human health. As a key substrate for the synthesis of glutathione (GSH), cysteine underpins one of the body’s central antioxidant defense systems. Glutathione is a tripeptide composed of cysteine, glycine, and glutamate; cysteine’s thiol group provides the active redox center that neutralizes reactive oxygen species, thereby protecting cells from oxidative damage. Adequate cysteine availability is rate‑limiting for glutathione synthesis, especially under conditions of increased oxidative stress, such as infection, aging, or environmental exposures. Beyond antioxidant defense, cysteine contributes to detoxification pathways in the liver, where it supplies sulfur for conjugation reactions that render xenobiotics and metabolic waste more water soluble for excretion. It also participates in protein folding and stability through disulfide bond formation, critical in structural proteins like keratin, which supports hair, skin, and nail integrity. Emerging research further implicates cysteine metabolism in weight regulation and energy homeostasis, with studies suggesting that dietary cysteine restriction activates metabolic pathways that may favor weight loss, highlighting its complex role in metabolic health. Additionally, cysteine is involved in immune function, supporting lymphocyte activity and phagocyte function through modulation of the intracellular redox environment. In clinical contexts, N‑acetylcysteine (NAC), a cysteine derivative, is used as a therapeutic agent for its mucolytic properties in respiratory conditions and as an antidote in acetaminophen overdose due to its ability to replenish glutathione stores. Systematic reviews of NAC supplementation indicate potential benefits in improving biochemical markers of liver function, although large‑scale trials are still needed to clarify effects on clinical outcomes. The thiol chemistry of cysteine also plays a role in metal ion binding, influencing the metabolism of iron, zinc, and copper, and may contribute to detoxification of heavy metals. Collectively, these mechanisms illustrate that cysteine’s functions extend well beyond basic protein synthesis to encompass redox regulation, detoxification, immune competence, and metabolic modulation.

Unlike essential amino acids, cysteine does not have a standalone Recommended Dietary Allowance (RDA) from NIH because the body can synthesize it from methionine. Instead, guidelines focus on combined intake of sulfur amino acids (methionine plus cysteine). International recommendations such as those by WHO suggest approximately 13 mg/kg body weight per day of combined methionine and cysteine to meet physiological needs. For a 70 kg adult, this equates to around 1.1 g per day. Protein‑rich diets typically provide sufficient sulfur amino acids to support both structural protein synthesis and maintenance of glutathione levels. Factors that may increase cysteine needs include aging, chronic illness, infection, smoking, and periods of rapid growth or recovery from injury, where oxidative stress and detoxification demands are elevated. Since cysteine synthesis from methionine requires adequate levels of vitamin B6 and folate, deficiencies in these cofactors can impair endogenous cysteine availability, necessitating attention to broader nutritional status. Clinical assessment of amino acid profiles or glutathione status may be indicated in specific scenarios such as metabolic disorders, malabsorption syndromes, or chronic disease. Despite the absence of a strict RDA, ensuring balanced protein intake with adequate sulfur‑containing amino acids is key for maintaining cysteine pools necessary for optimal health.

True dietary deficiency of cysteine alone is uncommon because it can be synthesized intracellularly from methionine, provided sufficient intake of methionine and B‑vitamin cofactors. However, states of inadequate sulfur amino acid availability or disruption of transsulfuration pathways can lead to low cysteine and glutathione levels. Clinical signs associated with low cysteine or glutathione include impaired antioxidant defenses, evidenced by increased oxidative stress and susceptibility to cellular damage. Individuals may experience chronic fatigue, weakened immune responses, and prolonged recovery from infections. Because glutathione is fundamental for detoxification, deficiency may present with signs of increased toxin burden, such as elevated markers of oxidative damage or impaired liver function tests. Some observational data link low cysteine and glutathione status with neurodegenerative conditions, though causal pathways remain under investigation. Inherited metabolic disorders affecting cysteine synthesis enzymes, such as cystathioninuria or homocystinuria, can present with biochemical abnormalities and systemic symptoms due to accumulation of intermediates and altered amino acid balance. Laboratory assessment of plasma cysteine, methionine, and glutathione can help delineate metabolic status, although reference ranges vary by assay and population. Clinicians should also consider cofactor deficiencies (e.g., vitamin B6) that impair cysteine synthesis, potentially exacerbating symptoms. While overt diseases caused solely by cysteine deficiency are rare, suboptimal cysteine and glutathione levels are associated with a range of conditions characterized by oxidative stress and impaired detoxification, underscoring the importance of adequate sulfur amino acid nutrition.

Dietary cysteine is found in protein‑rich foods, often reported as cystine (the oxidized dimer of cysteine) which the body can convert to cysteine. Analysis of USDA data shows the highest cystine content in animal sources such as roasted chicken leg (~740 mg per leg), lamb shoulder (~721 mg per 6 oz), and broiled pork tenderloin (~644 mg per 6 oz), making poultry and pork among the richest sources. Fish such as tuna and salmon also contribute significant amounts when consumed in typical portions. Among plant‑derived sources, oats, oat bran, lupin seeds, and legumes such as soybeans and black beans provide appreciable amounts, reflecting that sulfur amino acids are not exclusive to animal foods. Nuts and seeds, including sunflower seeds, walnuts, and pumpkin seeds, supply cysteine in plant‑based diets, although amounts per standard serving are lower than in concentrated animal proteins. Dairy products like cottage cheese and eggs (especially egg white and yolks) are moderate sources, combining quality protein with sulfur amino acids. Cysteine content varies widely among foods and depends on preparation and serving size; for example, one cup of cooked chicken breast may provide over 500 mg of cystine, whereas cereal grains contribute modest levels per cup. Combining diverse protein sources ensures adequate intake across dietary patterns, particularly for individuals following vegetarian or vegan diets who may rely more on legumes, seeds, and grains to meet sulfur amino acid needs.

Cysteine from dietary proteins is absorbed in the small intestine following proteolytic digestion. Cystine, the oxidized dimer form often reported in food composition data, is reduced to cysteine prior to absorption. Bioavailability depends on the protein matrix and presence of other amino acids; complete proteins such as those from animal sources tend to have higher digestibility compared to some plant proteins. Factors enhancing absorption include adequate intake of co‑nutrients such as vitamin B6, which supports enzymes in the transsulfuration pathway converting methionine to cysteine. Conversely, gastrointestinal disorders that impair protein digestion or absorption, such as celiac disease or inflammatory bowel disease, can reduce cysteine bioavailability. Once absorbed, cysteine enters systemic circulation and is taken up by tissues for protein synthesis and glutathione production. Because cysteine is also synthesized endogenously, dietary absorption complements internal production to maintain homeostasis. High sulfur diets may transiently elevate plasma cysteine, but regulatory mechanisms such as cysteine dioxygenase modulate hepatic catabolism to prevent excessive accumulation and potential cytotoxicity. Thus, both dietary intake and metabolic regulation determine tissue availability and functional utilization of cysteine.

Supplementation with cysteine per se is uncommon; more widely studied is N‑acetylcysteine (NAC), a cysteine derivative used clinically and as a dietary supplement to support glutathione synthesis. NAC serves as a cysteine donor and has been evaluated for its antioxidant and detoxification benefits, as well as potential to improve exercise performance and laboratory markers of oxidative stress. Systematic reviews of NAC supplementation show potential increases in albumin and decreases in bilirubin, suggesting effects on certain aspects of liver function, though evidence for broader clinical benefits requires further confirmation. Athletes and individuals under increased oxidative stress may consider NAC supplementation, but general population needs are typically met through balanced protein intake. When considering supplementation, it is important to select high‑quality products and consult healthcare professionals, especially in contexts of pregnancy, chronic disease, or medication use. In therapeutic settings, intravenous NAC is the standard of care for acetaminophen overdose due to its capacity to rapidly replenish glutathione. Oral NAC is also used for its mucolytic properties in respiratory conditions, and research exploring its roles in mental health, metabolic health, and age‑related oxidative stress is ongoing. Dose ranges in studies vary widely, but typical supplemental NAC doses are between 600 mg and 1,200 mg per day. It is important to weigh potential benefits against possible side effects, including gastrointestinal discomfort and rare interactions, and to tailor decisions to individual health status and goals.

There is no established tolerable upper intake level (UL) for cysteine from dietary sources because normal dietary patterns do not pose toxicity risks. Excessive intake of sulfur amino acids could theoretically lead to metabolic imbalances, but homeostatic mechanisms, including increased cysteine catabolism via cysteine dioxygenase, typically mitigate accumulation. Supplementation with derivatives like NAC has been associated with side effects at high doses, such as nausea, vomiting, and gastrointestinal discomfort, although serious toxicity is rare. High cysteine or cystine levels may contribute to conditions like cystinuria, where cystine crystals form in the urine, but this is related to genetic transporter defects rather than dietary excess. Because cysteine metabolism intersects with redox balance, theoretical concerns about pro‑oxidant effects at very high intracellular concentrations have been raised, although physiological relevance in humans remains unclear. In clinical practice, NAC toxicity is uncommon, but overdoses can produce adverse reactions including bronchospasm when inhaled or hypotension when administered rapidly intravenously, highlighting the need for medical supervision in therapeutic use. Thus, while dietary cysteine from foods is considered safe, supplements should be used judiciously and under guidance when intended for therapeutic purposes.

Cysteine itself is not known to have direct drug interactions at nutritional levels; however, its derivative NAC may interact with certain medications. NAC can affect the efficacy of nitroglycerin and related nitrates, potentially causing increased vasodilatory effects. It may also interact with activated charcoal, reducing NAC absorption when co‑administered. Because NAC modulates glutathione levels and redox status, it can influence the metabolism of drugs processed via hepatic pathways, although clinical significance varies. Individuals taking chemotherapeutic agents or immunosuppressants should consult physicians before initiating NAC supplementation. Moreover, high cysteine or NAC supplementation could theoretically influence insulin sensitivity and glucose metabolism, warranting caution in patients with diabetes. Healthcare providers should review all medications and supplements to avoid potential adverse interactions.

Common Forms: N‑acetylcysteine (NAC), L‑cysteine capsules

Typical Doses: 600–1,200 mg/day (NAC used in studies)

When to Take: With meals or as directed, based on purpose

Best Form: N‑acetylcysteine (for glutathione support)

⚠️ Interactions: Nitroglycerin (increased vasodilation), Activated charcoal (reduces absorption)