.L-CYSTEINE & N-ACETYL-L-CYSTEINE (NAC)
Written by Slawomir Gromadzki, MPH
Some experts believe that L-cysteine is one of the most underestimated natural food supplements because, as one experienced physician who recommended this powerful antioxidant to his patients wrote, “in certain cases, this supplement can make the difference between life and death.”
WHAT IS L-CYSTEINE
L-cysteine is a sulphur-containing amino acid and an important structural and functional component of proteins and enzymes found in our body. L-cysteine plays significant role in helping us to maintain normal body weight by promoting metabolism of fats. It promotes strong muscle tissue and immune system. It acts as an antioxidant; thus preventing oxidative damage and protecting internal organs including brain, liver and lungs. Cysteine also plays important role in the metabolism of essential biochemicals such as coenzyme A, heparin, and biotin.
AVAILABILITY OF L-CYSTEINE
Since L-cysteine can be produced in the liver, it is classified as a non-essential amino acid. However, at the same time it is also regarded as a conditionally essential because although it can be made in sufficient quantities under normal circumstances, modern stressful lifestyle, exposure to free radicals or toxins, sicknesses, and other factors greatly increase the demand for this vital amino acid. Also the concentration of cysteine in commonly consumed foods is too low to meet the demand.
Although L-cysteine can be produced in our body from an essential amino acid methionine, which we must get from food, yet the amount of dietary methionine is insufficient for the significant cysteine production. Moreover, taking methionine in the form of a supplement to increase cysteine is not recommended due to the fact that apart from being used in the body to make cysteine methionine is also converted to homocysteine, which significantly increases the risk factor for atherosclerosis, heart attacks and strokes. For this reason methionine supplementation is disqualified as the main source of cysteine.
Therefore, since we can’t get enough cysteine from our diet and because increasing methionine is not a healthy option; the only way of solving the common problem of cysteine deficiency is its direct supplementation.
Another reason our body experiences problems with manufacturing sufficient levels of L-cysteine can be deficiency of amino acid serine and some vitamins including folate, vitamin B6 and B12, as they are also required for the synthesis of L-cysteine.
L-CYSTEINE & GLUTATHIONE
The most important antioxidant to overall health and longevity in our body is glutathione as it detoxifies harmful chemicals into less damaging compounds, reduces oxidative damage caused by free radicals and even regenerates other antioxidants such as vitamin C or E. Glutathione is also critical for our immune system function and nerve signal efficiency.
Glutathione supplementation, however, has not been proven to be an effective way due to poor absorption and because it has low ability to accumulate in our brain.
Fortunately, L-cysteine has been shown an excellent ability to increase glutathione levels (>). The antioxidant activity of Glutathione (GSH) is attributed specifically to the presence and availability of this amino acid. Apart from cysteine our body requires two other amino acids – glutamate and glycine – in order to manufacture glutathione. Cysteine, however, is the most important among the three for proper synthesis of glutathione as it is a sulphur-containing amino acid that contributes to the sulfhydryl group in the glutathione molecule. This makes cysteine the most critical of the three building blocks for glutathione. It means that the concentration of cysteine in our body is the key factor determining the rate and amount of glutathione synthesis.
It is also important to know that vitamin B12, B6 and folate (folic acid) are critical for converting L-cysteine to glutathione. Unfortunately, since deficiency of the three vitamins (especially B12) is rampant today not only among vegans or elderly people, but even among those who consume animal products on a regular basis, it is very important to take vitamin B complex and 1000 mcg of sublingual vitamin B12 in the form of methylcobalamin every day after breakfast to make sure L-cysteine is properly converted to glutathione.
Cysteine is used to manufacture L-taurine which plays a key role in maintaining proper function of our central nervous system. Taurine also helps to regulate blood pressure, promote thermogenesis (fat burning), muscle building and eye health.
In high concentrations taurine is present in the heart to help regulate the heartbeat. Therefore, those who are low in taurine have higher risk of developing various heart problems including arrhythmia, palpitations or congestive heart failure. Taurine is also required for the conversion of glutamic acid into GABA (gamma-aminobutyric acid) which makes taurine very beneficial in improving mood and reducing risk of seizures caused by excess Glutamic acid building up in the brain.
NAC is a glutaminergic compound, because it can modulate levels of glutamate, the most abundant excitatory neurotransmitter (involved in learning, behaviour, and memory) in the brain which cause serious health issues if its levels are either too low or too high. NAC has been shown to increase glutamate when its too low and modulate the levels of excessive glutamate, which cause toxic damage in brain contributing to various neurological conditions including schizophrenia > and addiction >.
According to a 2020 research paper titled N-Acetylcysteine to Combat COVID-19 An Evidence Review, “N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2” (>).
NAC (N-Acetylcysteine) (600 to 1800mg a day) offers significant benefits at doses of 600 mg 2-3 times daily to boost most important body antioxidant – glutathione (strong immune system stimulator) and for individuals who have, or are at risk for coronavirus infection, chronic lung conditions such as COPD and IPF (idiopathic pulmonary fibrosis). In some cases, oral L-cysteine or NAC therapy has proved excellent for the treatment of asthmatics. NAC is also popular due to its “mucolytic” effect. It breaks up mucus in the respiratory tract by removing specific bonds in mucus proteins. It is able to break up or loosen sputum making it easier to cough up. A review of 40 clinical trials on NAC found that it was safe and effective as a natural treatment for chronic bronchitis. Because it helps reduce the viscosity (thickness) of sputum, NAC benefits ability to expectorate and to reduce the severity of coughs.
“We demonstrate that N-acetyl cysteine (NAC) reduces graphene oxide (GO) at room temperature. This represents a new green method to produce reduced GO (rGO). NAC adheres to the rGO surface as demonstrated by several spectroscopy techniques and avoids GO-mediated oxidation of glutathione. This method offers new opportunities for the production of green biocompatible rGO and NAC-based therapies.” >
L-CYSTEINE & LIPOIC ACID
Another reason to emphasise the importance of supplementing L-cysteine is the fact that apart from being the most vital factor required for the synthesis of glutathione in our body it is also used to make lipoic acid, regarded as the next most important antioxidant which is constantly praised by medical research for its remarkable health benefits.
BLOOD GLUCOSE LEVELS
Being a component of the hormone insulin L-cysteine is helpful in regulating blood glucose levels. A 2009 study showed that apart from lowering blood sugar L-cysteine supplementation was able to reduce the markers of vascular inflammation in patients with diabetes.
It is interesting that L-cysteine can be even converted in our body into glucose when blood glucose levels are too low. In this way L-cysteine helps prevent the unpleasant symptoms of hypoglycaemia (low blood glucose levels). At the same time this conversion may also enhance athletic endurance performance and prevent muscle catabolism.
HAIR & SKIN HEALTH
Supplementing L-cysteine is also frequently recommended for those who want to maintain strong and healthy hair and skin as this rich in sulphur amino acid is found in beta-keratin, the main protein in abundance in hair, nails and skin. It is therefore believed that L-cysteine deficiency can lead to various hair problems including hair loss and contribute to dandruff. Studies have shown L-cysteine can increase hair health and hair diameter.
Cysteine is important in collagen production, as well as skin elasticity and texture. It therefore plays an important role in maintaining healthy skin.
In addition, since L-cysteine is used in our body for the synthesis of glutathione and alpha lipoic acid, it indirectly helps maintain healthy skin by increasing these two antioxidants, regarded as most effective in slowing the ageing process.
SKIN LIGHTENING (WHITENING)
L-Cysteine or N-acetyl-cysteine (NAC) has been used for years to help treat asthma, lung disease, life-threatening liver failure from Tylenol overdose, or to prevent kidney damage from dyes used during x-ray studies. However, since L-cysteine has very good skin-whitening abilities, it is used in various anti-spot medicines and nutrition tablets. It stimulates pheomelanin production, a lighter skin pigment compared to eumelanin. At the same time, it represses the activity of tyrosinase enzymes which are involved in the production of melanin. L-cysteine is also one of the best ways to stimulate levels of Glutathione, body’s most powerful antioxidant with skin whitening-effect effect. Since it is impossible to get enough of this antioxidant from foods, the amount of supplemental L-cysteine needed for skin problems is about 200-500 mg a day. L-cysteine is not naturally present in food ingredients; the only natural form is L-cystine which in the body is converted to L-cysteine.
L-cysteine has been suggested as an antidote for the negative effects of excessive alcohol intake, such as liver damage or hangover. This effect of L-cysteine is the result of its ability to counteract the poisonous effects of acetaldehyde, which is a dangerous neurotoxin and by-product of alcohol metabolism in our body. L-cysteine helps convert acetaldehyde to the relatively harmless acetic acid. In one study, rats that were exposed to a lethal dose of acetaldehyde had very high survival rates after receiving L-cysteine.
SULPHUR & DETOXIFICATION
With regards to L-cysteine it is important to stress the fact that it is a sulphur-containing amino acid as sulphur is a very important element that is vital for healthy growth and metabolism. Sulphur is also one of the most effective detoxifying agents as it can bind to and expel from our body various harmful substances and chemicals including mercury, pesticides and other dangerous compounds and carcinogens.
Due to the fact that L-cysteine plays a critical role in the detoxification mechanisms in our body it can be used to help prevent liver damage and other harmful effects associated with toxic chemicals and drug reactions on its own and by increasing glutathione levels.
L-cysteine has been studied as a potential treatment for obsessive compulsive disorder (OCD) in children. The biochemical justification for using L-cysteine in OCD is based on the assumption according to which abnormal concentration of glutamate (regarded as excitatory neurotransmitter) in the brain may contribute to the disorder. And since L-cysteine has been found to effectively metabolise glutamate and lower its levels in the brain it is often recommended as a useful addition in the treatment of this condition.
Due to the same effect (improving glutamate metabolism), L-cysteine can be beneficial for people with bipolar disorder and schizophrenia, as excessive glutamate concentrations in the brain are suspected to have damaging effect on human brain, thus contributing also to schizophrenia and other mental disorders.
NAC (N-Acetylcysteine) (500 to 1000mg a day) offers significant benefits at doses of 600 mg 2-3 times daily for individuals who have, or are at risk for, chronic lung conditions such as COPD and IPF (idiopathic pulmonary fibrosis). In some cases, oral L-cysteine or NAC therapy has proved excellent for treatment of asthmatics. NAC is also popular due to its “mucolytic” effect. It breaks up mucus in the respiratory tract by removing specific bonds in mucus proteins. It is able to break up or loosen sputum making it easier to cough up. A review of 40 clinical trials on NAC found that it was safe and effective as a natural treatment for chronic bronchitis. Because it helps reduce the viscosity (thickness) of sputum, NAC benefits ability to expectorate and to reduce the severity of coughs.
OTHER HEALTH BENEFITS
It has been demonstrated that the gastrointestinal tract may be benefited by L-cysteine supplementation. It can be very beneficial especially for individuals who regularly use aspirin and other drugs which impose a damaging effect on the lining of the stomach and GI tract. It has been reported that L-cysteine helps prevent the damage by strengthening the lining of stomach and the entire GI tract.
Medical research has shown that L-cysteine supplementation combined with mesalamine can help reduce the symptoms of inflammatory bowel diseases (ulcerative colitis and Crohn’s disease).
L-cysteine is synthesized in our body to NAC which has been commonly used in the treatment of various respiratory conditions including bronchitis, tuberculosis, pneumonia, emphysema, cystic fibrosis as well as other conditions that result in the production of thick mucus. L-cysteine has the ability to break up mucus, thus making it easier to cough up phlegm that accumulates as a result of respiratory conditions. In addition, L-cysteine is recommended in respiratory diseases because it is also involved in strengthening the immune system.
L-cysteine is also commonly used in the paracetamol (acetaminophen) overdose treatment.
L-cysteine is essential for the immune system activation and T-cell production. According to one study by replenishing glutathione levels, L-cysteine appears to have beneficial impact on the immune function in individuals infected with HIV.
It has been discovered that by alleviating glutathione L-cysteine supplements may be effective in treating male infertility, if it is caused by oxidative stress which leads to DNA damage and poor semen quality. A 2016 study published in the International Journal of Fertility and Sterility found that the percentage of men able to induce pregnancy in the supplemented with L-cysteine group was over 30 percent higher.
Preliminary studies also show that L-cysteine may be useful in preventing or treating other conditions including colon and lung cancer, acne and angina (restricted blood flow to the heart). In some cases, oral cysteine therapy has proved excellent for treatment of asthmatics, enabling them to stop medications such as theophylline. It has clinical uses ranging from psoriasis to baldness. It has been used to prevent smoker’s hack. Cysteine was found to enhance the effect of topically applied silver or zinc salts in preventing dental cavities. It is believed that cysteine may also play an important role in the treatment of cobalt toxicity, psychosis, seizures or various types of cancer.
When taken as a supplement, Cysteine is offered in the form either L-cysteine or its modified form called N-acetyl-L-cysteine (NAC). Both of them, however, have basically the same health benefits and effect on our body.
L-CYSTEINE VS N-ACETYLCYSTEINE (NAC)
There are reasons to believe L-cysteine is a better and safer choice than NAC. First of all, NAC has been tested and approved for a very short-term use, and therefore it is impossible to guarantee its long-term use safety, as there is not enough data about it available to consider taking it on a long-term, everyday basis. On the other hand, L-cysteine has been examined far more extensively, and there is a lot of research data on L-cysteine available.
According to Durk Pearson and Sandy Shaw, independent experts in anti-ageing research and brain biochemistry, another very important reason L-cysteine should be regarded as superior to NAC is that “NAC can indiscriminately acetylate many compounds in our body, which is not desirable.”
Finally, the same above mentioned authors suggest that unlike NAC, L-cysteine is considered as a natural compound and therefore unlike NAC it is found in food. On the other hand, since NAC is an acetylated (in the lab) compound, which doesn’t exist in nature, or only in almost undetectable traces, it is considered as xenobiotic (not naturally found in the body). NAC is an occurring in our body amino acid only as a metabolite, derived from L-cysteine. Therefore, unlike L-cysteine which is found in most high-protein foods, NAC itself is not present in foods. That is also the reason why many people who know about this fact prefer to take L-cysteine instead of NAC.
On the other hand, the proponents of NAC claim that it is superior because L-cysteine can be also oxidised in our body to cysteine, thus contributing to the formation of kidney stones as a result of a long-term use. This problem, however, can be easily solved by taking L-cysteine with at least twice as much vitamin C which prevents oxidation of cysteine to cystine.
Supplements containing L-cysteine are often questioned by individuals following dietary restrictions such as Vegans, Vegetarians, and communities who are looking for halal, or kosher supplements, as the majority of L-cysteine products are obtained industrially by hydrolysis of animal materials, such as hog hair or poultry feathers. Look for L-cysteine supplements based on plant sources and suitable for vegans and vegetarians.
L-cysteine supplementation can be even more effective when used with vitamin C, vitamin E, vitamin B6, folic acid, sublingual methylcobalamin (form of B12) and selenium. Taking a good quality multivitamin-mineral formula will also improve the bioavailability of L-cysteine and help the liver to convert L-cysteine to glutathione.
DOSAGE AND SAFETY
Medical research shows that daily dosage of 500 to 1000mg of L-cysteine is perfectly safe and shouldn’t cause any side effects even if used for a long period of time. Only very high doses of more than 7 grams per day may be toxic and dangerous to human cells.
It is also suggested that individuals with cystinuria, a kidney condition in which too much cysteine is lost in the urine, should avoid cysteine supplements as it may lead to cysteine gallstones formation.
Individuals who are on the following medications are advised to consult a qualified practitioner before starting L-cysteine or NAC supplementation: Immuno-suppressants, Oxiconazole, Nitroglycerin and Isosorbide.
Activated charcoal shouldn’t be taken with L-cysteine or NAC as it may make them less effective.
Vida Mokhtari, Parvaneh Afsharian, Maryam Shahhoseini, et al (2017) A Review on Various Uses of N-Acetyl Cysteine. Cell J. 2017 Apr-Jun; 19(1): 11–17.
Adair JC, Knoefel JE, Morgan N. (2001) Controlled trial of N-acetylcysteine for patients with probable Alzheimer’s disease. Neurology. 2001; 57(8):1515-1517.
Ames BN. (2000) Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000; 889:87-106.
Badawy A, State O, Abdelgawad S. (2007) N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand. 2007; 86(2): 218-222.
Baines M et al. (2007) The Association between cysteine, bone turnover, an low bone mass; Calcif Tissu Int. 2007
Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res. 2000; 19(2): 205-221.
Chevez-Barrios P, Wiseman AL, Rojas E, Ou CN, Lieberman MW. (2000) Cataract development in gamma-glutamyl transpeptidase deficient mice. Exp Eye Res. 2000; 71(6):575-582.
Ciftci H, et. al. (2009). Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology. Volume 74, Issue, (pp. 173-6).
da Silva NP, de Souza FI, Pendezza AI, et al. (2013) Homocysteine and cysteine levels in prepubertal children: association with waist circumference and lipid profile. Nutrition. 2013; 29(1):166-171.
De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, et al. (2000) N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest. 2000; 30:915-929.
El-Hamamsy I, Stevens LM, Carrier M, et al. (2007) Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. J Thorac Cardiovasc Surg. 2007 Jan; 133(1):7-12.
Ghabril M, Chalasani N, Björnsson E. (2010) Drug-induced liver injury: a clinical update. Curr Opin Gastroenterol. 2010 May; 26(3): 222-226. Review.
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. (2000) Case-control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer. 2000; 89:376-382.
Eck HP, Gander H, Hartmann M, et al. (1989) Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe Seyler 1989; 370:101-8.
Jain SK. (2012) L-cysteine supplementation as an adjuvant therapy for type-2 diabetes. Can J Pysiol Pharmacol. 2012; 90(8): 1061-1064.
Kozer E, Koren G. (2001) Management of paracetamol overdose: current controversies. Drug Saf. 2001; 24(7): 503-512.
Mazer M, Perrone J. (2008) Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol. 2008 Mar; 4(1):2-6. Review.
Muller F, Svardal AM, Nordoy I, Berge RK, Aukrust P, Froland SS. (2000) Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest. 2000; 30(10): 905-914.
National Center for Biotechnology Information. PubChem Compound Database; CID=5862, https://pubchem.ncbi.nlm.nih.gov/compound/5862 (accessed Apr. 19, 2017).
Novelli EL, Santos PP, Assalin HB, Souza G, Rocha K, Ebaid GX, et al. (2009) N-acetylcysteine in high-sucrose diet-induced obesity: energy expenditure and metabolic shifting for cardiac health. Pharmacol Res. 2009 Jan; 59(1):74-79.
Ozkilic AC, Cengiz M, Ozaydin A, Cobanoglu A, Kanigur G. (2006) The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. J Basic Clin Physiol Pharmacol. 2006; 17(4):245-254.
Pol and Lebray. (2002) N-Acetylcysteine for paracetamol poisoning: effect on prothrombin. Lancet 360:1115 (2002).
Safarinejad, M and Safarinejad, S. (2009). Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. The Journal of Urology. Volume 18, Issue 2, (pp. 741-51).
Salim AS. (1993) Sulfhydryl-containing agents in the treatment of gastric bleeding induced by nonsteroidal anti-inflammatory drugs. Can J Surg 1993; 36:53-8.
ScienceDaily: Targeting oxidized cysteine through diet could reduce inflammation and lower disease risk; Mar. 31, 2009
Silva LA, Silveira PC, Pinho CA, Tuon T, Dal Pizzol F, Pinho RA.(2008) N-acetylcysteine supplementation and oxidative damage and inflammatory response after eccentric exercise. Int J Sport Nutr Exerc Metab. 2008 Aug; 18(4):379-388.
Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. (2000) The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000 Aug; 16(2):253-262.
Sutherland ER, Crapo JD, Bowler RP. (2006) N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease. COPD. 2006;3(4):195-202.
Tolar J, Orchard PJ, Bjoraker KJ, Ziegler RS, Shapiro EG, Charnas L. (2007) N-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy. Bone Marrow Transplant. 2007; 39(4):211-215.
“Why We Take Cysteine Rather Than N-Acetylcysteine”, The Durk Pearson & Sandy Shaw, Life Extension News, Volume 5 No. 5 October 2002: http://www.life-enhancement.com/magazine/article/790-why-we-take-cysteine-rather-than-n-acetylcysteine—jan–2003