L-CYSTEINE

BACKGROUND

Ingredient Type: Amino Acid

Also Known As: L-2-Amino-3-mercaptopropionic acid, L-Zystein, N-acetyl-L-cysteine (NAC), Acetyl Cysteine, Acétyl Cystéine, Acetylcysteine, Acétylcystéine, Cysteine, Chlorhydrate de Cystéine, Cysteine Hydrochloride, Hydrochlorure de Cystéine, Cystine, L-Cysteine,, L-Cysteine HCl, NAC, N-Acetil Cisteína, N-Acetyl-B-Cysteine, N-Acétyl Cystéine, N-Acétylcystéine, N-Acetylcysteine

L-cysteine, a form of cysteine, is an amino acid categorized as a semi-essential amino acid in humans. It indicates that an adequate amount of l cysteine is biosynthesized by the body under normal circumstances. It needs methionine which is helpful for the supply of sulfur required for its amino acid synthesis. There are several animal and human sources, such as human hair, goose and duck feathers, hooves, and swine bristles that are used to derive L-cysteine. Other food-related sources may include dairy products, Brussels sprouts, sprouted lentils, broccoli, garlic, and oats.

The high reactivity of L-cysteine makes it one of the most effective and essential elements in biochemical reactions. Particularly, it undergoes redox reactions, which provide strong antioxidant properties to support cells from damage.

 

 

TRADITIONAL USES

In the Middle Ages, food rich in L-cysteine provided many benefits related to general health. It is traditionally used to harden arteries and treat arthritis. People in ancient times used this non-essential amino acid for the treatment of lung diseases, including emphysema, bronchitis, and tuberculosis. People back in the time also used L-cysteine for baking purposes as well, for instance, gluten softening, dough relaxing, dough conditioning, reduced fermentation times, and better dough consistency (11).

History shows that its deficiency is usually caused in infants and the elderly. People with metabolic syndrome and malabsorption issues are less likely to synthesize l-cysteine in an adequate amount. Hence, people used to opt for dietary sources to cope with their deficiency. Nowadays, it is also available in a supplemented form, such as powders, tablets, and fluids.

 

Science-Backed Evidence

L-Cysteine and Anti-Cancer

Cancer develops when cells divide uncontrollably and invade new tissues. Changes in DNA can cause cancer as well. The TNM (tumor, lymph nodes, and metastases) approach is used by clinicians to diagnose the most prevalent kinds of cancer. Chemotherapies, surgeries, or radiation treatments are the sole options for treating uncontrollable cancer. However, a few complementary therapies or therapeutic substances, such as L-cysteine, can prevent cancer in its early stages.

According to a study, the effects of L-cysteine were analyzed in the human bladder cells by exhibiting anticancerous impact. This study also identified bladder cancer cell lines and molecular mechanisms. In this study, clonogenic assay and Cell Counting Kit‑8 assay were used to measure cell proliferation. Flow cytometry analyzed apoptosis and cell cycle. Western blotting was used to determine cell cycle‑associated proteins and apoptosis expression levels. It was observed that treatment with L cysteine inhibits colony formation and proliferation in bladder cancer cells. Apoptosis was also enhanced by L-cysteine. Hence, it was proved that L-cysteine has an anticancerous effect on bladder cancer cells and can be used as a potential therapeutic agent in the treatment of cancer (1).

According to another study, L-cysteine was synthesized in-situ, which were capped lanthanum hydroxide nanoparticles. They are also stated as Cys-La(OH)3 NPs for the non-invasive analysis of oral cancer. Different techniques were used in this study, including scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and electrochemical techniques. These L-cysteine-capped lanthanum hydroxide nanoparticles were deposited electrophoretically onto an indium tin oxide. It was also utilized for anti-cytokeratin fragment-21-1 (anti-Cyfra-21-1) immobilization which was carried out in order to detect Cyfra-21-1 electrochemically. With a reaction time of five minutes, this immunosensor exhibits a wide detection range of 0.001–10.2 ng mL-1, a low detection limit of 0.001 ng mL-1, and a high sensitivity of 12.044 A. Comparing this immunosensor to previously reported biosensors and commercially available ELISA kits, it was discovered to be more advanced in terms of high sensitivity and low detection limits (Kinesis DX). L-cysteine in this study was used to present a new pathway to fabricate diagnostic devices which are highly sensitive and biocompatible. It was concluded that these amino acid-capped lanthanum hydroxide nanoparticles can be used for the fabrication of diagnostic devices (2).

In an article, N-acetyl-L-cysteine (NAC) was used to inhibit H2O2-mediated cell death and to check the effect on apoptosis. It has been shown that the non-toxic doses and 10 and 20 mM L- cysteine has the tendency to improve fisetin (FIS)-mediated apoptosis in colon cancer cells. Treatment by using L-cysteine boosted PAPR protein and cleaved caspase-3 expression compared to treatment with FIS alone and resulted in a higher density of DNA ladders. With the stimulation of caspase 9 protein cleavage, NAC decreased the mitochondrial membrane potential of colon cancer cells that had been exposed to FIS. By utilizing particular antibodies and Western blotting, colon cancer cells treated with FIS and L-cysteine (NAC) demonstrated a strong suppression of the phosphorylation of the ERK protein compared to those treated with FIS or NAC. Additionally, NAC enhanced a chemical chrysin-related FIS-related apoptosis in colon cancer cells, and it sensitized these cells to FIS-related apoptosis. It was concluded that the application of FIS and NAC as a therapy to treat colon cancer is well therapeutic and encouraged due to the relevant evidence to support NAC sensitizing human colon cancer cells to FIS-induced apoptosis (3).

 

Support of L-Cysteine for the Brain

The brain is one of the body’s most intricate and important organs, controlling things like emotions, vision, appetite, touch, thought, and memory that manage the body. Any brain issue results in poor body regulation and control, which eventually has an impact on overall health and wellbeing. A chemical called L-cysteine has the tendency to raise glutathione levels in the brain. It also improves memory and other brain-related abilities.

According to an article, the effect of the antioxidant L-cysteine (Cys) was investigated to observe the activity of the brain of rats induced with streptozotocin (STZ) diabetes. In this study, 38 male Wistar rats were used and split into 6 different groups. All rats with diabetes were treated with STZ injections when the experiment was initiated. However, groups treated with L-cysteine were given injections of Cys 7 mg/kg body weight. Spectrophotometrically, the brains of the rats were measured. There is a significant reduction in brain activity in diabetic patients. AChE activity was increased due to diabetes. However, the administration of L cysteine further enhanced it. The current data indicated that L-cysteine has a protective role against diabetes’ oxidative effect on the brain of the adult rat. Additionally, a rise in whole-brain AChE activity brought on by diabetes was observed, and this rise was exacerbated by L-cysteine. Untreated diabetes may have an impact on metabolic energy production, neuronal excitability, and certain neurotransmission systems through the suppression of K+-ATPase, Na+. These in-vitro results on the use of L-Cys as a neuroprotective drug against diabetes may be suggestive of a potential protective role. It was concluded that L-cysteine is a highly potential agent for therapeutic treatments for the brain (4).

According to a study, preincubation of brain homogenates was investigated with L-cysteine (Cys), L-phenylalanine (Phe), and reduced glutathione (GSH) which has the tendency to reverse the effects of the free radicals. It was observed that when brain homogenates were preincubated with 0.83 m l cysteine or glutathione, the enzymatic inhibition was entirely reversed, and the TAS value increased by 150-180%. According to some theories, L-cysteine and GSH’s antioxidant effects result from free radicals adhering to their sulfhydryl groups, preventing them from inhibiting the Na+, K+-ATPase. Additionally, L-cysteine and GSH could control metabolic energy production toward normal levels and neuronal excitability, which may be hampered by free radical action on Na+, and K+-ATPase. Therefore, it was concluded that L-cysteine has a protective effect on rat brain Na+, K+-ATPase inhibition induced by free radicals (5).

The study reveals the effect of L-cysteine in neonatal hypoxic-ischemic (HI) injury. In the brain, cystathionine-β-synthase (CBS) catalyzes L-cysteine. The goal of the study was to determine whether endogenous H2S released by L-Cysteine may lessen acute brain injury and enhance neurobehavioral outcomes in newborn mice. By suppressing caspase-3 activation, reducing the Bax/Bcl-2 ratio, and declining Akt and ERK phosphorylation, L-cysteine treatment significantly decreased infarct volume and brain edema and ultimately reduced the risk of neuronal cell death. L-cysteine also markedly increased the expression of heme oxygenase-1 and NF-E2-related factor 2. Additionally, L-cysteine reduced the production of pro-apoptotic proteins linked to endoplasmic reticulum stress. A significant improvement was observed in the neurobehavioral outcomes after treating with L-cysteine against HI-induced injury in neonates (6).

 

L-Cysteine and Fertility

During infertility, a person is unable to conceive after a year of trying. Endometriosis, thyroid problems, and uterine fibroids are a few examples of female infertility causes. Low sperm counts or testosterone levels may be observed in men with fertility complications. Additionally, the likelihood of infertility rises with age.

In a study, N-acetyl-L-cysteine (NAC) was used to examine its effect on male fertility. In the clinical trial, 35 infertile men were included and divided into 2 groups, including the NAC-treated group of 15 men and the control group of 20 men. Protamine content and semen parameters were assessed before and 3 months after varicocelectomy. Results indicated that there was a significant decrease in protamine shortage, DNA fragmentation, oxidative stress, and the percentage of aberrant semen parameters in both groups after surgery than they were before. The outcomes were compared between the groups by calculating the percentage of improvement in each of these measures compared to before surgery for each group. The only significant differences between the NAC and control groups were the percentage of protamine insufficiency and DNA fragmentation. It was indicated that L-cysteine (NAC) improved fertility rate and chromatin integrity among these participants. L-cysteine was considered one of the most significant substances for the treatment of male infertility (7).

Another study investigated fertility and embryonic development in SD male and female rates through NAC. 100, 300, and 1000 mg kg−1 day−1 doses were given to these rats. In females, infertility was analyzed before mating to embryogenesis. There was no significant effect of NAC on the reproductive capability of the male rats. The oocytes and embryos were assessed morphologically to clarify the cause of the effects of NAC. The unfertilized oocytes (UO) recovered from the ampullae of the uterine tubes and Gestational Day (GD) 1 and 2 embryos recovered from the oviducts or uterus of the rats that received NAC i.e., at a dosage of 1000 mg kg−1 day−1 for more than 1 week before mating was assessed morphologically by stereomicroscope. Morphometric evaluation calculated zona pellucida (ZP) thickness. In the NAC group, ZP-lacking oocytes, and partially lacking were identified. On GD1, each animal’s number of embryos significantly decreased, and in the NAC group, no embryos were retrieved on GD2. The NAC-treated oocytes with altered ZP were aberrant or nonviable. The results of this investigation point to a connection between alterations in the ZP and the sterility brought on by NAC (L-cysteine) (8).

 

 

 

Diabetes and L-Cysteine

Diabetes is a persistent (long-lasting) health disease that concerns how the body converts meals into energy. With diabetes, the body either doesn’t make enough insulin or can’t use it as efficiently as it should. Most of the food eaten is turned into sugar (also called glucose) and delivered into the bloodstream. Diabetes is a chronic medical condition that can be controlled but often remains for a lifetime. However, L-cysteine is considered an effective, essential in the balance of diabetes.

In this study, the combination of metformin with L-cysteine was analyzed to provide benefits in reducing inflammation, oxidative stress, and insulin resistance. To analyze all the factors of type 2 diabetes mellitus, streptozotocin-induced type 2 diabetes in rats was used. A high-fat diet (HFD) was given to male Wistar rats for around 8 weeks for the induction of insulin resistance. Right after this, they were known to be diabetic with low doses of streptozotocin. L-cysteine with a quantity of 300 mg/kg per day and metformin with a 300 mg/kg dose per day was given for two additional weeks to the diabetic rats. Normal rat chow was given to the control rats. Homeostasis model assessment-insulin resistance index (HOMA-IR), fasting blood glucose, serum free fatty acids, and fasting serum insulin were measured at the end of the treatment. The liver was also isolated and used to analyze reduced glutathione, malondialdehyde, cytochrome c levels, and caspase-3. Results indicated that l cysteine with the combination of metformin improved insulin resistance. Significant decreases in oxidative stress, serum FFAs, and inflammatory parameters were observed in all the groups treated with L-cysteine and metformin compared to untreated control groups. It was concluded that metformin associated with L-cysteine has stronger effects to manage type 2 diabetes (9).

In this aforementioned aritcle, the effect of the antioxidant L-cysteine (Cys) was investigated to observe the activity of the brain of rats induced with streptozotocin (STZ) diabetes. In this study, 38 male Wistar rats were used and split into 6 different groups. All rats with diabetes were treated with STZ injections when the experiment was initiated. However, groups treated with L-cysteine were given injections of Cys 7 mg/kg body weight. Spectrophotometrically, the brains of the rats were measured. There is a significant reduction in brain activity in diabetic patients. AChE activity was increased due to diabetes. However, the administration of L cysteine further enhanced it. The current data indicated that L-cysteine has a protective role against diabetes’ oxidative effect on the brain of the adult rat. Additionally, a rise in whole-brain AChE activity brought on by diabetes was observed, and this rise was exacerbated by L-cysteine. Untreated diabetes may have an impact on metabolic energy production, neuronal excitability, and certain neurotransmission systems through the suppression of K+-ATPase, Na+. These in-vitro results on the use of L-Cys as a neuroprotective drug against diabetes may be suggestive of a potential protective role. It was concluded that L-cysteine is a highly potential agent for therapeutic treatments for diabetes (4).

 

SAFETY

Interactions

• Interaction with Nitroglycerine: Blood vessels can be dilated by nitroglycerine, and it may also enhance blood flow. Taking it with the combination of L-cysteine may cause dizziness, headache, and fatigue.
• Moderate interaction with activated charcoal: When someone takes too much acetaminophen or another prescription, activated charcoal may be administered to prevent toxicity. These drugs may become bound to activated charcoal in the stomach, preventing absorption by the body. When used with activated charcoal, N-acetyl cysteine may lessen its effectiveness in avoiding poisoning (10).
• Medications Interaction for high blood pressure (ACE inhibitors): The amino acid N-acetyl cysteine may lower blood pressure. If it is combined with N-acetyl cysteine with blood pressure drugs, the blood pressure may drop too low. Captopril (Capoten), ramipril (Altace), lisinopril (Zestril, Prinivil), enalapril (Vasotec), and other drugs are used to treat high blood pressure.
• Chloroquine (Aralen): Malaria is treated with the medication Chloroquine (Aralen). By creating an accumulation of heme inside of cells, it kills malaria. N-acetyl cysteine may stop heme from amassing inside cells. This could lessen the effects of the drug chloroquine (11).

 

Side Effects

L-cysteine is more likely to be safe when taken for health benefits. However, there are a few adverse effects noticed in some research including vomiting, constipation, diarrhea, and nausea. It may also lead to fever, drowsiness, headache, liver problems, and low blood pressure (12).

 

 

 

 

 

 

 

 

 

 

 

References

1. Ho, J. N., Kang, M., Lee, S., Oh, J. J., Hong, S. K., Lee, S. E., & Byun, S. S. (2018). Anticancer effect of S‑allyl‑L‑cysteine via induction of apoptosis in human bladder cancer cells. Oncology Letters, 15(1), 623-629.
2. Tiwari, S., Gupta, P. K., Bagbi, Y., Sarkar, T., & Solanki, P. R. (2017). L-cysteine capped lanthanum hydroxide nanostructures for non-invasive detection of oral cancer biomarker. Biosensors and Bioelectronics, 89, 1042-1052.
3. Wu, M. S., Lien, G. S., Shen, S. C., Yang, L. Y., & Chen, Y. C. (2014). N‐acetyl‐L‐cysteine enhances fisetin‐induced cytotoxicity via induction of ROS‐independent apoptosis in human colonic cancer cells. Molecular carcinogenesis, 53(S1), E119-E129.
4. Zarros, A., Liapi, C., Galanopoulou, P., Marinou, K., Mellios, Z., Skandali, N., … & Tsakiris, S. (2009). Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase,(Na+, K+)-and Mg2+-ATPase: modulation by L-cysteine. Metabolic brain disease, 24(2), 337-348.
5. Tsakiris, S., Angelogianni, P., Schulpis, K. H., & Behrakis, P. (2000). Protective effect of L-cysteine and glutathione on rat brain Na+, K+-ATPase inhibition induced by free radicals. Zeitschrift für Naturforschung C, 55(3-4), 271-277.
6. Liu, S., Xin, D., Wang, L., Zhang, T., Bai, X., Li, T., … & Wang, Z. (2017). Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: role of oxidative stress and endoplasmic reticulum stress. Redox biology, 13, 528-540.
7. Barekat, F., Tavalaee, M., Deemeh, M. R., Bahreinian, M., Azadi, L., Abbasi, H., … & Nasr-Esfahani, M. H. (2016). A preliminary study: N-acetyl-L-cysteine improves semen quality following varicocelectomy. International journal of fertility & sterility, 10(1), 120.
8. Harada, M., Kishimoto, K., Furuhashi, T., Naito, K., Nakashima, Y., Kawaguchi, Y., & Hiraoka, I. (2003). Infertility observed in reproductive toxicity study of N-acetyl-L-cysteine in rats. Biology of reproduction, 69(1), 242-247.
9. Salman, Z. K., Refaat, R., Selima, E., El Sarha, A., & Ismail, M. A. (2013). The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats. European journal of pharmacology, 714(1-3), 448-455.
10. Sameem, B., Khan, F., & Niaz, K. (2019). l-Cysteine. In Nonvitamin and Nonmineral Nutritional Supplements(pp. 53-58). Academic Press.
11. Otagiri, M. (2005). A molecular functional study on the interactions of drugs with plasma proteins. Drug metabolism and pharmacokinetics, 20(5), 309-323.

De Vries, N., & De Flora, S. (1993). N‐acetyl‐l‐cysteine. Journal of cellular biochemistry, 53(S17F), 270-277.