Cysteine

Cysteine is a nutrient belonging to the essential amino acid class.

Cysteine is also known as L-Cysteine, 2-Amino-3-sulfhydrylpropanoic acid, L-Cys and L-Cystine.

Cysteine is vital for protein structure, antioxidant defence, detoxification, immunological function, collagen formation, enzyme activity, and overall cellular health.

Cysteine deficiency can cause symptoms, which include mood swings, insomnia, low serotonin, depression, anxiety, and decreased cognitive ability.

Cysteine may be found naturally in various meals high in protein from both plant and animal sources. Foods like broccoli, brussels sprouts, cauliflower, legumes, cereals, whole grains, nuts and seeds are examples of plant sources, whereas products like meat (pork, beef, chicken and turkey), egg whites, and dairy (milk, yoghurt and cheese) are examples of animal sources.

Cysteine is absorbed in the small intestine, distributed widely for protein synthesis and antioxidant activities, metabolized into glutathione and taurine, and excreted in the urine as sulfur-containing metabolites.

The common side effects of Cysteine include generalized flushing, fever, nausea, and warm sensation.

Cysteine is available in tablets, capsules, oral powders and injection solutions.

Biochemical action of Cysteine

Cysteine, belonging to the essential amino acid class, acts in several biological processes. It works via glutathione synthesis and redox reactions pathway.

Cysteine is generally produced in the human body when adequate methionine is present. Cysteine is an antioxidant that participates in redox processes. Cysteine's antioxidant effects are typically characterized by the tripeptide glutathione, which exists in humans and other creatures. Because of its limited systemic availability, glutathione (GSH) is usually synthesized from its constituent amino acids, cysteine, glycine, and glutamic acid. Cysteine's redox activity is critical for maintaining cellular redox balance. It affects NF-B signalling, which affects immunological responses and inflammation. Cysteine also influences NMDA receptors, affecting synaptic plasticity and memory. Its involvement in the cystine/glutamate antiporter promotes cysteine availability for glutathione production. These functions indicate cysteine's role in oxidative stress management, immunological responses, and brain processes.

Cysteine is available in tablets, capsules, oral powders and injection solutions.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.
• Injection solutions: To be administered parenterally, as applicable.

Cysteine can be used as a supplement when the cysteine taken through diet is insufficient.

Taking cysteine supplements effectively treats cysteine deficiency caused by specific genetic diseases or other disorders.

Cysteine supplements are commonly used to reduce diarrhoea in people with cholera who receive antibiotics.

Supplemental cysteine may be essential in supporting the body's healing processes.

Cysteine helps in the growth and repair of muscles when taken as a supplement.

Supplemental cysteine's antioxidant properties could benefit athletes and physically active individuals by reducing the oxidative stress produced by exercise.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Cysteine can help to support as a supplement for the following health benefits:

• Antioxidant: Cysteine functions as a free radical scavenger, preventing oxidative stress-related cellular damage and boosting antioxidant activity by protecting glutathione. Increasing glutathione levels reduces ageing, helps prevent or treat several medical disorders, and promotes immunological function. Supplementing with cysteine may also improve immune responses when glutathione and cysteine deficiencies are prevalent.
• HIV: Cysteine's capacity to strengthen your immune system has been demonstrated in studies with HIV patients. According to one European study, a formulation that contained NAC, bovine colostrum, omega-3 fatty acids, and a combination of vitamins and minerals reduced the loss of immune cells. Another study revealed that L-cysteine appears to have immune-mediated function in HIV-positive individuals by restoring glutathione levels.
• Detoxification: Cysteine can reduce the effects of hazardous substances and medication interactions. According to a study published in the Alternative Medicine Review, the body's detoxification processes depend heavily on cysteine. Supplemental cysteine helps replenish glutathione levels depleted by the pro-oxidative effects of toxic metals so that you can effectively detoxify toxins.
• Male Fertility: Cysteine is an excellent therapy for impotence in males with poor semen quality, DNA damage, and oxidative stress. It is administered to prevent glutathione depletion during oxidative stress.
• Digestive Health: Cysteine has the potential to reduce the ageing process and enhance the body's digestive abilities. Gastroenteritis and low stomach acid are two digestive problems that are more common as people age. Having free radicals in the body may be the cause of this. Studies suggest that taking cysteine supplements helps lessen the signs and symptoms of ulcerative colitis, an inflammatory bowel condition that results in persistent inflammation and ulcers in the digestive tract.
• Respiratory Health: The antioxidant enzyme glutathione peroxidase, which protects the lungs from oxidative stress and hazardous environmental stimuli, possesses cysteine as one of its components. For people with respiratory disorders like asthma, this supplement may be beneficial.
• Immune support: Cysteine boosts the immune system by stimulating the formation of white blood cells, essential for protecting the body from infections and disease. Also, it helps in controlling immunological responses and maintaining a healthy immune system.

Cysteine supplementation may be administered orally and parenterally.

Orally: Cysteine supplements are available as tablets, capsules and powders that can be taken orally. To maximise absorption and reduce the possibility of gastrointestinal discomfort, it is advisable to take cysteine supplements with meals.

Parenterally: The injection solution of cysteine is usually given intravenously (IV) directly into a vein. Cysteine injection is administered to adults and kids with severe liver disease who may need TPN due to possible impairment of their enzymatic activities.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 500 mg, 1000 mg
• Capsules: 220mg, 500mg, 600mg
• Powder, oral: 100g, 125g, 200g
• Injectable solutions: 50 mg/mL, 100 mg/mL

Dosage Adjustment for Adult Patients

Stable patients

Recommended protein requirement: 0.8-1 g AA/kg/day

Recommended dose: 7 mg/g AA

Recommended volume: 0.14 mL/g AA

Critically ill patients

Recommended protein requirement: 1.5-2 g AA/kg/day

Recommended dose: 7 mg/g AA

Recommended volume: 0.14 mL/g AA

Cysteine should be a supplement that helps in several biological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.

• Stay within your daily calorie needs.

• Keep away from high-protein meals and beverages, especially those that include other amino acids, since these may hinder the absorption of cysteine.

• When using cysteine supplements, avoid high-protein diets or sulfur-rich foods like allium and cruciferous vegetables as they could increase sulfur amino acid intake and potential adverse effects.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of Cysteine is 4 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of Cysteine is not established.

Cysteine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to sulfur-related allergies
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Post-surgery
• Pulmonary edema
• Acidosis due to low cardiac output
• Homocystinuria
• Susceptible to cystine kidney stones.
• Active peptic ulcer disease
• Hyperammonemia

High-dose supplements should be used cautiously in pregnancy, breastfeeding and the elderly.

Before taking cysteine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent negative effects.

Cysteine supplements may give a false-positive result in the nitroprusside test for ketone bodies, which is used to diagnose diabetes.

In patients with low hepatic or renal function, IV-AA infusion may cause an increase in BUN.

Individuals with existing gout may use cysteine cautiously as it can affect uric acid levels.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

Caution is advised when consuming alcohol with Cysteine.

There is no sufficient scientific evidence traceable regarding the use and safety of Cysteine for breastfeeding populations.

While taking cysteine supplements, limit the consumption of foods that are high-protein diets or sulfur-rich foods like allium and cruciferous vegetables, as they could increase sulfur amino acid intake and potential adverse effects.

The adverse reactions related to cysteine can be categorised as:

• Common: GI disturbances like bloating, gas, nausea, diarrhoea and vomiting
• Less Common: Allergic reactions (rash, itching).
• Rare: Severe allergic reactions (anaphylaxis)

The clinically relevant drug interactions of cysteine are summarized here:

• Antidiabetes drugs: Cysteine may help to reduce blood sugar levels. Taking Cysteine with diabetic treatments may cause blood sugar to fall too low. Monitor closely the blood sugar levels.
• Vitamin C: It may inhibit the oxidation of L-cysteine to L-cystine.
• Zinc: When used concurrently, cysteine complexes with zinc and may increase its absorption.
• Acetaminophen: Cysteine may alter the metabolism of acetaminophen. It is advisable to separate doses when taken.

The common side of Cysteine includes the following:

• Generalized flushing
• Fever
• Vomiting
• Bloating
• Gas
• Upset stomach
• Nausea
• A warm sensation, redness, inflammation of veins, and blood clots at the infusion site

Cysteine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of Cysteine for pregnant populations. Avoid Cysteine supplements unless advised to do so by a healthcare professional while pregnant.

• Paediatrics:

To meet the nutritional needs of newborn newborns (particularly preterm neonates), cysteine injection is used. However, there haven't been any appropriate studies conducted to date that haven't shown issues specific to children that would restrict the usage and safety of cysteine in paediatric populations.

Dosage Adjustment for Paediatric Patients

Preterm and term infants (aged below 1 month)

Recommended protein requirement: 3-4 g AA/kg/day

Recommended dose: 22 mg/g AA

Recommended volume: 0.44 mL/g AA

1 month to less than a year

Recommended protein requirement: 2-3 g AA/kg/day

Recommended dose: 22 mg/g AA

Recommended volume: 0.44 mL/g AA

1 to less than 12 years

Recommended protein requirement: 1-2 g AA/kg/day

Recommended dose: 22 mg/g AA

Recommended volume: 0.44 mL/g AA

12 to 17 years

Recommended protein requirement: 0.8-1.5 g AA/kg/day

Recommended dose: 7 mg/g AA

Recommended volume: 0.14 mL/g AA

• Geriatrics: There is no sufficient scientific evidence traceable regarding the use and safety of Cysteine for geriatric populations. Avoid Cysteine supplements unless advised to do so by a healthcare professional.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of Cysteine for lactating mothers populations. Avoid Cysteine supplements unless advised to do so by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Cysteine. Overconsumption of Cysteine may lead to symptoms that might include gastrointestinal discomfort like nausea, diarrhoea, vomiting, disruption of sulfur amino acid balance and allergic reactions.

There is no specific antidote or treatment for excessive intake of supplemental Cysteine.

Cysteine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after Cysteine supplement use or dietary intake. Fluid intake should be increased along with electrolyte monitoring. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Cysteine

The cysteine has a thiol group (-SH) attached to it in the chemical structure. This thiol group enables cysteine to form disulfide bonds essential for protein folding and maintaining structural integrity.

Due to reduced sulphur's chemical characteristics, cysteine serves various biological purposes. Sulphide is a potent nucleophile and a highly reactive mediator of redox processes. These include catalysis, the activation of reactive groups (like coenzyme A), disulfide bonds with their structural and regulatory roles, and, in particular, electron transfer via iron-sulfur clusters.

Cysteine is produced from serine and homocysteine through the transsulfuration process, which uses vitamin B6 as a cofactor. Additionally, it serves as a precursor for the antioxidant glutathione, which is essential for cellular defence against oxidative stress. The methionine and homocysteine cycles act significantly in cysteine metabolism.

Kinetic profile:

• Absorption: Cysteine is absorbed in the small intestine via active transport pathways and is used for utilization in various metabolic reactions once absorbed.
• Distribution: Cysteine circulates throughout the body and is essential for protein synthesis, antioxidant defence, and other critical processes. Its unique sulfur-containing structure results in the formation of disulfide bonds in proteins, enhancing their structural stability.
• Metabolism: Cysteine's involvement expands to the production of potent antioxidant glutathione, which protects cells from oxidative damage. The sulfur atom in cysteine is critical for glutathione's antioxidant properties. It also produces taurine, which is utilized in a variety of processes.
• Elimination: Cysteine is not eliminated in significant quantities by the body. Instead, metabolites containing sulfur, such as sulfate and taurine, are eliminated in urine.

1. https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf

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4. Fahey R.C. Biologically important thiol-disulfide reactions and the role of cyst(e)ine in proteins: An evolutionary perspective. Adv. Exp. Med. Biol. 1977;86:1–30.