Does L-Cysteine Have Health Benefits? The Studies Reviewed

Introduction

Cysteine is a sulfur-containing amino acid that is made by our bodies and used as a building block for proteins.

Although classified as a non-essential amino acid, in rare cases, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption diseases.

Us humans can (and do) also acquire cysteine through the consumption of protein rich foods such as chicken, beef, fish and eggs.

L cysteine is a form of cysteine. There are lots of claims made by the supplement industry to convince consumers to part with their hard earned cash. Right now, L cysteine supplementation is being widely promoted for anti-aging, liver detoxification, boosting immune function, male fertility and preventing or treating several health conditions.

There are many websites that provide a whole lot of hype but only varying degrees of accuracy of information about L cysteine. Pretty much all of these websites are selling the product… and so obviously have a vested interest in convincing the general public that this amino acid needs to be bought.

Unlike many supplements, there have been many studies to assess the effects of L cysteine supplementation, and the results are certainly interesting. This article will look in depth at the evidence, claims and effects of this amino acid.

What Is L-Cysteine And Why Is It Important?

Without delving deep into biochemistry, all amino acids exist in two isomers (compounds with the same composition of atoms but in different arrangements within the molecule and different properties as a result), D-stereo-isomers and L-stereo-isomers.

L cysteine is a cysteine isomer. N-acetylcysteine (NAC) is a variant of L-cysteine and it is very important because it has anti-oxidant and anti-inflammatory properties and is a glutathione precursor‬‬‬‬‬. Both NAC and glutathione are antioxidants, and are popular for their ability to minimize oxidative stress (1).

In fact, glutathione is currently one of the most studied antioxidants. This is likely due to it is made throughout the body and it is basically found in all cells, sometimes in rather high concentrations (2).

When cysteine is taken as a supplement, it is usually in the form of NAC. Although not all mechanisms underlying the biological activities of NAC are established, it has an important role in the body with the ability to detoxify oxidizing radicals and bind redox-active metal ions (3).‬‬‬‬

Researchers think that free radicals play a role in aging as well as the development of a number of diseases. Antioxidants fight free radicals, which are compounds in the body that damage cell membranes and DNA. NAC is a powerful antioxidant as it acts directly as a scavenger of free radicals, especially oxygen radicals (4).

NAC has been in clinical practice for several decades. It has been used as a mucolytic agent (breaks down mucus) and for the treatment of drug reactions and toxic metals and pollutants, respiratory issues such as bronchitis, HIV/AIDS, and psychiatric disorders.

Is There Any Research?

YES! A lot of thorough research has been conducted to assess the use of L-cysteine supplementation as a therapy for many conditions. There are 1607 search results for L cysteine clinical trials in PubMed, which is a decent body of research. Of these, 1531 related to clinical trials in humans (9).

Clinical trials of cysteine supplementation have been conducted for skin disorders, hair loss, asthma, bronchitis, allergies, cystic fibrosis, chronic obstructive pulmonary disease, heavy metal toxicity, iron deficiency, diabetes & diabetic nephropathy, seizure disorders, reducing cytotoxic treatment side effects, HIV infection, and alcoholism.

Many of these have shown benefit, but most require further research to have a solid evidence base. When cysteine is taken as a supplement, it is usually in the form of NAC.

Does L-Cysteine Improve Male Fertility?

It is estimated that approximately 30-80% of infertility cases are caused by oxidative stress and decreased level of seminal antioxidant capacity (5).

NAC can scavenge free radicals and improve the viscosity and elasticity of semen, which are important for fertility (6). Some studies have shown that combinations of supplements have improved sperm quality and decreased infertility, for instance in conjunction with selenium, but these have not isolated the effects of NAC alone (4).

A recent preliminary study looked into the effect of NAC on semen quality and fertility following varicocelectomy (surgery to correct variocele) (5). The results of this study revealed that NAC improved chromatin integrity and the resulting pregnancy rate when administered post-surgery.

This blinded clinical trial was conducted with 35 infertile men with varicocele. Due to the limited number of cases however, further study is warranted. The evidence is too weak to be conclusive at present.

Bottom Line: Not at present…. but possibly in the future…. The preliminary evidence is far too weak.

Is It An Antioxidant?

Effective regulation of the balance between oxidation and anti-oxidation is very important for the functioning of our cells and maintaining our DNA. Supplementation with antioxidants attempts to minimize oxidative stress.

NAC has anti-inflammatory properties. It is also a glutathione precursor and direct antioxidant. NAC and glutathione are both antioxidants, and are popular for their ability to minimize oxidative stress (2).

In fact, glutathione is currently one of the most studied antioxidants. This is likely due to it being synthesized all throughout the body and it is basically found in all cells, sometimes in fairly high concentrations (2).

Antioxidants fight free radicals, which are compounds in the body that damage cell membranes and DNA. NAC is thought to help combat disease and help the liver detoxify a wide range of toxic metals and pollutants.

Several clinical studies have reported on the use of NAC as an antioxidant (2). Although not all mechanisms underlying the biological activities of NAC are established, it has an important role in detoxifying oxidizing radicals and binding redox-active metal ions.

Bottom Line: Yes, It is.

Does It Detoxify?

There is considerable clinical evidence to support the fact that oral and intravenous NAC are equally effective in the prevention of hepatotoxicity (chemical driven liver damage) (3).

Doctors often give intravenous (IV) NAC to people who have taken an overdose of acetaminophen, to help prevent or reduce liver and kidney damage. Acetaminophen poisoning is a medical emergency and can happen because of an accidental overdose. If you think someone has taken an overdose of acetaminophen, take them to the hospital!

Unfortunately there is no research to suggest that NAC will help a hangover.

Bottom Line: Yes. NAC is thought to help the liver detoxify a wide range of toxic metals and pollutants. It has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose.

Does It Balance Blood Sugar Levels?

Diabetes is a chronic metabolic disorder that is a major and growing worldwide health problem. NAC has been hypothesized as a potential therapy to maintain blood sugar within normal ranges.

There are many reports on effects of antioxidants in the management of diabetes. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development.

An analysis of the findings of more than 100 papers relating to the actions of NAC demonstrated that NAC supplementation has some positive effects during the inflammatory process in insulin resistance.

Moreover, NAC can modulate certain signaling pathways in both insulin target cells and β cells, which are both involved in blood sugar regulation. The diverse biological effects of NAC may make it a potential therapeutic target in modulating blood sugar in the treatment of type-2 diabetes.

However researchers noted that further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity. At this stage, the evidence is not strong enough to show a strong effect of NAC. Much of the research has shown an effect in animal models such as rats. In the future, this needs to be replicated in large-scale controlled human trials.

Interestingly, it has been reported that circulating levels of L-cysteine and its oxidised forms correlate with body mass index and obesity. However, researchers noted that it is unclear whether this is a causal or consequential factor, and whether the observed differences in circulating L-cysteine reflect differences in cysteine intake or metabolism.

Further work is required to investigate whether the mechanisms responsible for these effects can be used therapeutically.

Bottom Line: Weak evidence. 

Does It Relieve Symptoms Of Respiratory Conditions?

NAC has  ‬been  ‬used  ‬since the 1960’s  ‬as  ‬an ‬ adjuvant therapy for several respiratory ‬conditions, due to its mucolytic (ability to break down mucus) properties. ‬‬‬‬‬‬‬‬‬‬‬‬‬

A thorough review of the 39 clinical trials to date, with a total of 2,011 patients found that NAC may help relieve symptoms of chronic bronchitis, leading to fewer flare ups (5). It concluded that, for treatment periods of approximately 12-24 weeks, oral NAC improved symptoms in patients with chronic bronchitis compared with placebo, without increasing the risk of adverse effects but was ambivalent about whether this benefit was sufficient to justify the routine and long-term use of NAC in all patients with chronic bronchitis. Again, with limited evidence, further studies are required.

NAC is known to have anti-oxidant and anti-inflammatory properties, which have been shown an uncertain benefit in chronic obstructive pulmonary disease (12) (COPD) patients ( 6, 7).

A systematic review of the literature on the use of NAC in treating influenza (13) looked at series of studies that demonstrated the anti-viral effects of NAC on influenza pneumonia, but notes that the effects are limited to certain strains only and that further research needs to be done (8).

The study notes that NAC is thought to have contributed to the successful treatment of patients infected with H1N1, but that additional research is needed to determine which human influenza strains are most responsive to NAC treatment (4).

Beyond being a mucolytic, more evidence is needed to support its use in relieving respiratory conditions.

Bottom Line: Yes, but only for some respiratory conditions. 

Does It Support Digestive Health?

Oxidative stress is considered as one of the factors involved in several signals and symptoms of inflammatory bowel diseases.

A recent review of all the research into the use of antioxidant therapy on inflammatory bowel diseases analysed a whopping 134 papers (14); however of these, only four were conducted in humans. The review identified very weak evidence to suggest that NAC may be effective in treating these diseases.

Most studies into the effectiveness in NAC in digestive health have been limited to rats. Researchers stated that “the alternative antioxidant therapy to inflammatory bowel disease seems promising and must be further and continuously investigated, especially, in clinical trials” (9).

The evidence is far too weak at this stage to suggest a benefit to digestive health.

Bottom Line: Very weak evidence.

Does It Promote Hair Growth?

Bottom Line: No evidence exists to suggest that NAC promotes hair growth.

Does It Help Treat Psychiatric Disorders?

Over the past decade, NAC has been investigated as a novel treatment for a wide range of psychiatric disorders and a few neurological disorders. Studies suggest that NAC is a favorable treatment for some disorders but more evidence is needed (15).

A thorough recent review of all the human trials using NAC as a treatment to improve psychiatric and neurological disorders found favorable but only limited evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer’s disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy (10).

A total of 65 publications met the inclusion and exclusion criteria for this review.

Further larger confirmatory studies are needed to provide a stronger evidence base as a treatment for psychiatric disorders.

Bottom Line: Weak evidence. 

Is L-Cysteine Safe?

Used since the 1960’s, NAC has been considered as fairly well tolerated, but it must be used judiciously and under medical supervision. Studies have shown no maternal or fetal harmful effects of NAC treatment (4).

Gastrointestinal symptoms have been commonly reported adverse effects, including nausea, vomiting, and diarrhea. Neurological side effects have also been commonly reported including headaches and tingling. Dermatological adverse effects, elevated blood pressure, fatigue, muscle pains, insomnia, nasal congestion, runny nose, restlessness, dizziness and vivid dreams and irritability have also been reported.

According to the University of Maryland Medical Center, cysteine supplements can interact with several medications, including those that suppress the immune system (such as prednisone and azathioprine); chest pain medications (nitroglycerin and isosorbide); antifungal medication used for athlete’s foot (oxiconazole) and activated charcoal (11).

Because of the potential for side effects and interactions with medications, supplements should only be taken under the supervision of a knowledgeable doctor..

Here’s why….. NAC may raise levels of homocysteine, an amino acid that is associated with heart disease.

Very high doses (more than 7 grams) of cysteine may be toxic to human cells and may even lead to death.

Intravenous administration of NAC to treat acetaminophen poisoning may cause severe allergic reactions, and these people should not take cysteine supplements (for cystinuria, a kidney condition in which too much cysteine is lost in the urine) (16).

When inhaled into the lungs, NAC may cause tightness in the chest, numbness of the mouth, runny nose, and drowsiness (16). This may make asthma symptoms worse therefore asthmatics who are taking NAC should be closely monitored by their doctors.

Conclusion

Unlike many popular supplements, there has been a lot of research into the effects of L cysteine supplementation, and the results are certainly interesting.

NAC has been in clinical practice since the 1960’s. It has been used as a mucolytic agent and for the treatment of drug overdose.

NAC treatment appears safe, tolerable and affordable when used judiciously and under medical supervision.

However, data is still limited in terms of quantity and quality of studies for many of the disorders despite showing some evidence of a beneficial effect for some disorders. Further well designed, larger controlled trials are needed for different psychiatric, gastrointestinal and respiratory disorders.

In addition, studies to elucidate which of its many mechanisms of action are responsible for its efficacy are required.

It’s a potential medication worth exploring further, but it needs a stronger evidence base to justify taking it at present beyond a mucolytic agent and drug overdose treatment.

References

  1. https://www.spectracell.com/media/uploaded/s/0e2040911_supplement-cysteine.pdf
  2. Kerksick C, Willoughby D. The Antioxidant Role of Glutathione and N-Acetyl-Cysteine Supplements and Exercise-Induced Oxidative Stress. Journal of the International Society of Sports Nutrition. 2005;2(2):38-44. doi:10.1186/1550-2783-2-2-38.
  3. The chemistry and biological activities of N-acetylcysteine. Samuni Y1, Goldstein S, Dean OM, Berk M.  Biochim Biophys Acta. 2013 Aug;1830(8):4117-29. doi: 10.1016/j.bbagen.2013.04.016. Epub 2013 Apr 22.
  4. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A Review on Various Uses of N-Acetyl Cysteine . Cell Journal (Yakhteh). 2017;19(1):11-17.
  5. Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: An evidence based review. International Journal of Reproductive Biomedicine. 2016;14(12):729-736.
  6. Barekat F, Tavalaee M, Deemeh MR, et al. A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy. International Journal of Fertility & Sterility. 2016;10(1):120-126.
  7. Lasram MM1, Dhouib IB2, Annabi A2, El Fazaa S3, Gharbi N4. A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin Biochem. 2015 Nov;48(16-17):1200-8. doi: 10.1016/j.clinbiochem.2015.04.017. Epub 2015 Apr 25.
  8. Elshorbagy, A. K., Smith, A. D., Kozich, V. and Refsum, H. (2012), Cysteine and Obesity. Obesity, 20: 473–481. doi:10.1038/oby.2011.93
  9. Suddarth  SB.  ‬‬Acetylcysteine, a new  ‬and ‬ effective  mucolytic  agent.  ‬Bull  Geisinger. ‬ 1963 May;15:‬65–‬‬9.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬
  10. Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000 Aug;16(2):253-262.
  11. Decramer M1, Rutten-van Mölken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donno M, De Backer W, Lankhorst I, Ardia A. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005 Apr 30-May 6;365(9470):1552-60.
  12. Sutherland ER, Crapo JD, Bowler RP. N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease. COPD. 2006;3(4):195-202.
  13. Casanova T, Garigliany M. N-Acetylcysteine: An Old Drug With Variable Anti-Influenza Properties. J Controversies Biomed Res 2016; 2(1):1–8. Doi: http://dx.doi.org/10.15586/jcbmr.2016.13
  14. Moura, F., Andrade, K., Santos, J., Araujo, O., Goulart, M. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work? Redox Biology Volume 6 Pages 617-639.
  15. Deepmala1, Slattery J2, Kumar N3, Delhey L2, Berk M4, Dean O4, Spielholz C5, Frye R2. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 2015 Aug;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015. Epub 2015 May 6.
  16. http://www.umm.edu/health/medical/altmed/supplement/cysteine
Summary
Does L-Cysteine Have Health Benefits? The Studies Reviewed
Article Name
Does L-Cysteine Have Health Benefits? The Studies Reviewed
Author
Healthy But Smart

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