NAC-n-Acetylcysteine

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n-aC 600

28/10/23

n-Acetylcysteine and its benefits

N-Acetylcysteine or NAC is the N-Acetyl derivative of the non-essential sulphur amino acid L-Cysteine; the N-acetylated form is more stable and more available to the body. NAC is well known as an antidote to paracetamol, in cases of intoxication due to this drug, as it is a precursor of the antioxidant par excellence: glutathione, a key enzyme cofactor in oxidation processes.

It is very often used for symptoms of the respiratory tract as a mucolytic, thus useful in severe colds due to its marked ability to 'fluidify' the upper airways.
Also in the clinical field, there is a great deal of research that sees it involved in numerous neuroprotective and hepatoprotective processes.
So many aspects that correlate with numerous biological systems!

RECCOMMENDED DOSAGE:
Almost all studies reported in this article confirm that dosages from 600 mg up to 4000 mg are considered safe for counteracting the pro-oxidant effects on the body. Oral supplementation shows a plasma peak 2-3 hours after intake and with a half-life of around 6 hours, so the best times to take it are away from training or in the morning/evening on a rest day. We recommend taking it with plenty of water at mealtimes.

N-AC & SPORT

High-intensity exercise is certainly one of the predisposing factors for the formation of free oxygen radicals, which are highly toxic products for our organism and are created in relation to the degree of oxidative stress generated in our cells.

The balance between reactive species and detoxification systems is crucial for maintaining homeostasis between eustress and distress. A decline in immune function by the athlete with repeated high-intensity exertion over time with reduced recovery time between training sessions and their mesocycles may lead to risks of decreased performance, infections, decline in cognitive ability and high risk of injury.

Often the athlete 'stressed' by excessive high-impact physical activity has compromised anti-oxidant defence systems, leading to a more abrupt decline in performance and an onset of chronic adrenal fatigue. The supplementation of N-AC in a randomised double-blind study with control + placebo for 9 days (1200 mg/day) in 10 well-trained triathletes demonstrated an improvement in cycling performance through better redox balance, improving exercise tolerance and thus promoting adaptive processes (1).

Indeed, N-AC supplementation improved cycle ergometer sprint simulation sessions by minimising the oxidative damage induced by high-intensity exercise. In contrast, a randomised controlled trial evaluated the acute effect of N-AC supplementation on physical performance in semi-professional players of rugby, a high-impact, high-intensity sport (2).

Seventeen players were given 1000 mg of NAC or Placebo for 6 days. After analysing exercise tests typical of the discipline to assess the effects of the supplementation, the researchers concluded that the effects on performance were unclear and at times irrelevant; instead, it reduced markers of post-traumatic impact inflammation and improved recovery, but only for the first few days of intake. On days 5-6 of intake, however, an increase in muscle inflammation was observed. These results are unclear and too non-specific to draw any interesting conclusions.

A more recent review and meta-analysis has re-evaluated the beneficial effects of N-AC in sports subjects (3), more so pointing out that some studies have largely exceeded the recommended dosage limit up to daily doses of 5800 mg with an increase in side effects, which however remain unclear in relation to the subjectivity of response. Although more studies have been done in the literature on N-AC intake in sport to date, research still remains sceptical about its potential role in improving performance. Undoubtedly, since it has an anti-oxidant property, it is more logical to assume that the benefits reported by athletes on performance can be attributed to fewer inflammatory markers. Many more studies will be needed to confirm its efficacy.

N-AC AND THE RESPIRATORY SYSTEM

Taking N-AC was seen to be effective in improving respiratory function in subjects with MPCO (chronic obstructive pulmonary disease) (4). 120 patients with the disease were divided into 2 groups: 1 group taking N-AC and 1 group taking placebo.

1200 mg of N-AC divided twice daily (600+600) for a full year improved the worsening of the disease and fewer post-healing relapses, and also confirmed a reduction in hospitalisation days compared to the placebo control group.

This result revealed the validity of using N-AC in subjects with chronic bronchitis or respiratory diseases to prevent oxidative stress damage caused by an immune system deficit. Higher levels of N-AC showed strong mucolytic and fluidifying activity protecting the body from endogenous and exogenous pathogens and toxic agents. Confirming this hypothesis, a very recent review (5) from 2020 collected 41 studies in which N-AC supplementation was above 600 mg/day with peaks of up to 3 g/day in evaluating the efficacy and safety of this dosage against respiratory diseases. The safety profile was high and standardised at both 600 mg and 3000 mg dosages, confirming that N-AC remains a molecule of first choice against these diseases.

N-AC AND NEURODEGENERATION

Being a powerful antioxidant, its effect has also been found to be positive in neurodegenerative diseases. A 2018 study (6) confirmed that dosages of 600 to 6000 mg/Die (very high dosages!) gave positive effects in alleviating symptoms in Parkinson's and Alzheimer's disease. Indeed, one of the benefits of N-AC is that it modulates certain key neurotransmitters for excitatory function such as glutamate. Glutamate plays an important role in pain perception, mood control, learning and mnemonic function in the individual. Its dysfunction is often the cause of cognitive decline and the development of neurodegenerative diseases. Thanks to N-AC, this important neurotransmitter is efficiently regulated in order to maintain homeostasis of its expression.

N-AC AND THE SEXUAL SPHERE

In men suffering from infertility, sperm function is impaired due to oxidative stress, which can adversely affect sperm production as it can cause DNA damage. A study involving 50 infertile men aged between 25 and 40 years (7) found supplementation with 600 mg/Die of N-AC for 3 months to be a valuable aid in combating this problem.The evaluation of blood parameters of the main hormonal markers of reproductive origin, seminal parameters and total antioxidant capacity confirmed the improvement of sperm profiles both in terms of count and motility, a pronounced antioxidant capacity and a restoration of LH, FSH, testosterone and prolactin hormone values. The scientists at the end of the research also added an important piece of information, namely that the problem of infertility is often associated with a deficiency of minerals and/or vitamins in addition to N-AC (vitamin C-A-E, carnitine, folate, zinc and selenium).

N-AC AND LIVER

Its hepatoprotective role is derived from its ability to generate glutathione, the body's most powerful antioxidant. Glutathione is a tri-peptide made up of Cysteine, Glutamic Acid and Glycine, which protects against free radicals and has a strong detoxifying activity due to its ability to chelate, i.e. bind to itself, heavy metals that are toxic to the body by eliminating them from the body. N-AC seems to be the key molecule in the process of glutathione generation. Glutathione helps our liver in cell regeneration processes (already a biological effect of hepatocytes) especially in situations of alcoholism or liver fatigue from drugs such as paracetamol overdose (which produces adverse effects on the liver at high dosage). It is also useful for sportspeople on a high-protein diet.

N-AC E COVID-19

In order to protect those who have not yet contracted SARS-Cov-2, N-AC at dosages of 600 mg could be an excellent economical and effective strategy to prevent potential infection (8). In the presence of early symptoms such as fever or a dry cough, a dosage doubled to 1200 mg/day seems to accelerate recovery and minimise symptoms. Patients who have already contracted Covid-19 can test an inhalable formulation with a nebuliser, but the oral form also seems to provide excellent benefits.

N-AC can therefore increase intracellular glutathione synthesis in T lymphocytes and block apoptosis during viral infections and influenza, especially with high dosages at 2400 mg/day divided into 2 doses of 1200 mg each.

The study recommends a venous injection at higher grades of disease: 600 mg for early febrile or cough symptoms, 1200 mg for dyspnoea or pneumonia, venous injection at 100 mg/kg/day for acute respiratory distress syndromes and venous injections of 150 mg/kg/day for diseases of multiple biological systems (multiple organs). Clearly, the use of other antioxidant/antiviral agents can only improve recovery and lung ventilation while reducing mortality.

Dr. Frisoni Nicola

Bibliografia

1) Slattery KM, Dascombe B, Wallace LK, Bentley DJ, Coutts AJ. "Effect of N-acetylcysteine on Cycling Performance following Intensified Training.", Med Sci Sports Exerc. 2014

2) Kate Rhodes and coll. "Acute effect of oral N-AcetylCysteine on muscle soreness and exercise performance in semi-elite rugby players", J Diet Suppl 2019

3) Kate Rhodes, Andrea Braakhuis "Performance and side effect of supplementation with N-Acetylcysteine: a systematic review and meta-analysis", 2017 Sports Medicine

4) Tse HN, Raiteri L, Wong KY, Ng LY, Yee KS, Tseng CZ. "Benefits of high dose N-acetylcysteine to exacerbation-prone COPD patients.", Chest. 2014 May 15.

5) Peter Calverley & coll. "Safety of N-Acetylcysteine at high doses in chronic respiratory diseas: a review", Drug Saf. 2020

6) Giuseppe Tardiolo, Placido Bramanti and Emanuela Mazzon. "Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases", Molecules 2018,

7) Jannatifar R, Parivar K, Roodbari NH, Nasr-Esfahani MH. "Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men.", Reprod Biol Endocrinol. 2019

8) Z. Shi & Puyo A.C. "N-Acetylcysteine to combat Covid-19: an evidence review", Ther Clin Risk Manag 2020

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