The antioxidant, called PharmaNAC, contains pharmaceutical-grade N-acetylcysteine and is specially-packed to preserve its potency. PharmaNAC lowered irritability in children with autism as well as reduced the children’s repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial.

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Irritability affects 60 to 70 percent of children with autism. “We’re not talking about mild things: This is throwing, kicking, and hitting; the child needing to be restrained,” said Antonio Hardan, MD, the primary author of the new study. “It can affect learning, vocational activities and the child’s ability to participate in autism therapies.”

The study appears in the June 1 issue of Biological Psychiatry. Hardan is an associate professor of psychiatry and behavioral sciences at Stanford and director of the Autism and Developmental Disabilities Clinic at Packard Children’s.

Finding new medications to treat autism and its symptoms is a high priority for researchers. Currently, irritability, mood swings and aggression, all of which are considered associated features of autism, are treated with second-generation antipsychotics. But these drugs cause significant side effects, including weight gain, involuntary motor movements and metabolic syndrome, which increases diabetes risk. By contrast, side effects of PharmaNAC are generally occasional and mild, with gastrointestinal problems such as constipation, nausea, diarrhea and decreased appetite. Most people report no side effects. It is easy for children to take because the PharmaNAC tablet is dropped into a small glass of water to make a fizzy drink, so the child can take it without having to swallow a pill or capsule.

The state of drug treatments for autism’s core features, such as social deficits, language impairment and repetitive behaviors, is also a major problem. “Today, in 2012, we have no effective medication to treat repetitive behavior such as hand flapping or any other core features of autism,” Hardan said. PharmaNAC could be the first medication available to treat repetitive behavior in autism — if the findings hold up when scrutinized further.

The study tested children with autism ages three to 12. They were physically healthy and were not planning any changes in their established autism treatments during the trial. In the double-blind study design, children received PharmaNAC or a placebo of identical appearance and taste for 12 weeks. The product used was the effervescent, pharmaceutical-grade preparation donated by BioAdvantex Pharma Inc., the manufacturer.

Subjects were evaluated before the trial began and every four weeks during the study using several standardized surveys that measure problem behaviors, social behaviors, autistic preoccupations and drug side effects.

During the 12-week trial, PharmaNAC treatment decreased irritability scores from 13.1 to 7.2 on the Aberrant Behavior Checklist, a widely used clinical scale for assessing irritability. The change is not as large as that seen in children taking antipsychotics. “But this is still a potentially valuable tool to have before jumping on these big guns,” Hardan said.

In addition, according to two standardized measures of autism mannerisms and stereotypic behavior, children taking PharmaNAC showed a decrease in repetitive and stereotyped behaviors.

“One of the reasons I wanted to do this trial was that NAC is being used by community practitioners who focus on alternative, non-traditional therapies,” Hardan said. “But there is no strong scientific evidence to support these interventions. Somebody needs to look at them.”

Hardan cautioned that the NAC for sale as a dietary supplement at drugstores and grocery stores differs in some important respects from the individually packaged doses of pharmaceutical-grade NAC used in the study, and that the over-the-counter version may not produce the same results as PharmaNAC. “When you open the bottle from the drugstore and expose the pills to air and sunlight, it gets oxidized and becomes less effective,” he said.

Although the study did not test how PharmaNAC works, the researchers speculated on two possible mechanisms of action. PharmaNAC increases the capacity of the body’s main antioxidant network, which some previous studies have suggested is deficient in autism. In addition, other research has suggested that autism is related to an imbalance in excitatory and inhibitory neurotransmitters in the brain. PharmaNAC could modulate the glutamatergic family of excitatory neurotransmitters, which might be helpful in autism.

The scientists are now applying for funding to conduct a large, multicenter trial in which they hope to replicate their findings.

“This was a pilot study,” Hardan said. “Final conclusions cannot be made before we do a larger trial.”

“BioAdvantex is delighted with the promise that this research shows for PharmaNAC in treating irritability and repetitive behaviours in children with autism,” said David Aiello, President, BioAdvantex Pharma. “We are committed to continuing to support research of this condition which affects many Canadians, both adults and children.”

Hardan’s collaborators at Stanford were Lawrence Fung, MD, a psychiatry resident; Robin Libove and Surekha Nair, MD, social science research assistants; postdoctoral scholar Tetyana Obukhanych, PhD; Lenore Herzenberg, DSc, professor of genetics and member of the Stanford Cancer Institute; and Rabindra Tirouvanziam, PhD, a former instructor in pediatric pulmonary medicine at Stanford who is now at the Emory University School of Medicine.

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Information about the Stanford Autism Center at Packard Children’s Hospital and the Department of Psychiatry and Behavioral Sciences, which also supported the research, is available online at http://autism.lpch.org and http://psychiatry.stanford.edu.

Thiolex Development Corporation has exclusively licensed the technology behind the use of N-acetylcysteine in autism to BioAdvantex Pharma Inc., a related company.

When we exercise our bodies are put under stress, working overtime to repair any damage or injury we’ve done.  While many other high-dose antioxidants have been proposed to help athletes recover, many have been shown limit training adaptations due to their interference with the cell signaling that is necessary to adapt to higher intensity training..  NAC, however, does not have this effect because in increases the synthesis of glutathione only when there is a demand for it in the body and only when the oxidative stress in the body demands it.

NAC’s role in increasing levels of the antioxidant glutathione in the body makes it an excellent way to strengthen the immune system.  For athletes, though, the antioxidant-boosting properties of N-acetyl cysteine are especially important, helping to reduce cell damage, speed up the body’s recovery from injury, and aid in muscle growth.  Moreover, recent studies suggest that NAC supplementation might increase the amount of time that athletes can do intensive physical exercise.  For endurance athletes such as triathletes, long-distance runners, and cyclists this is especially important news.

Remember: athletes (and anyone else) looking to supplement with NAC should take caution to ensure that the NAC supplement they choose is a high-quality, safe, and effective formulation.

At the foundation of this research into NAC and IPF is the fact that glutathione levels are depleted due to increased oxidant burden in the lung tissue of IPF patients.  Because NAC increases glutathione levels, researchers reasoned, supplementation with NAC should improve patients’ lung function; this is precisely what they found.  Both of the studies discussed below used an effervescent NAC tablet available in Europe, similar to PharmaNAC in the US and Canada.

One double-blind study randomly assigned 182 IPF patients to receive either 600 mg of NAC 3 times per day or placebo for one year (in addition to standard therapy of prednisone and azathioprine).  After the twelve months were up, NAC was found to decrease the mean loss of vital capacity by 9% and of carbon monoxide diffusing capacity by 24%, when compared to placebo, and mortality was 9% in the NAC group as compared to 11% in the placebo group.  No significant differences were found in severity of adverse reactions to treatment between groups with the exception of a lower rate of myelotoxic medication side effects in the group supplementing with NAC.

A similar study conducted in Germany administered oral N-acetyl cysteine to IPF patients, who before the supplementation were found to have glutathione levels that had been reduced to about 51% of those observed in normal individuals.  This study again confirmed the safety and efficacy of NAC as a glutathione precursor.  While many studies investigate the use of inhaled NAC, this study found that while aerosol (inhaled) NAC raised glutathione levels in the lungs for only a few hours, by administering NAC orally the increased glutathione concentrations remained present up to 10 hours after the last dose.  The researchers concluded that oral supplementation with NAC may be a rational therapy to reverse glutathione deficiency in the lower respiratory tract of IPF patients in order to restore the antioxidant balance and to control fibroblast proliferation.  The finding that no adverse affects were found with long-term NAC therapy combined with the understanding that glutathione deficiency may play a central role in IPF led these researchers to suggest long-term oral supplementation of NAC for IPF patients.

N-acetylcysteine for idiopathic pulmonary fibrosis.  Alan R. Gaby

The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis.  A. Meyer, R. Buhl, H Magnussen.

What is COPD?

Chronic obstructive pulmonary disease, or COPD, is a progressive disease affecting patients’ ability to breathe.  COPD is not an isolated health issue—it is the 4^th leading cause of death in the US, more than 12 million people are diagnosed with it, and an additional 12 million likely have COPD but don’t know it.

The symptoms of COPD develop slowly and worsen over time, limiting patients’ ability to do even everyday activities such as walking.  Those who suffer from COPD experience a cough that is accompanied by excessive mucus, wheezing, shortness of breath, and tightness in the chest.

There is no medical cure for COPD yet.  However, according to recent research there is evidence that NAC can help COPD patients breathe better, stay active, and slow the progression of the disease.

COPD is broken down into two forms, Chronic bronchitis and Emphysema. Chronic bronchitis is characterized by long term coughing with associated mucus.  Emphysema is characterized by lung destruction through inflammation caused by various environmental stress factors such as smoking. 

The picture below shows a case of emphysema and the damage to the alveoli (breathing sacs where O₂ and CO₂ are exchanged on the membrane walls) in the lungs. As shown the membrane walls are degraded making it more difficult to get enough O₂ in and CO₂ out of the lungs causing a need for harder breathing.  The damage is the result of the influx of superoxide molecules causing a redox imbalance and thus thinning and destruction of the walls.  The result is fewer and larger alveoli that have reduced surface area and lower pressure, decreasing the amount of possible gas exchange to occur. This may result in symptoms such as wheezing, shortness of breath, and chest tightness.

Chronic Bronchitis is also the result of lung irritation and inflammation.  In this case the membrane walls tend to thicken and allow mucus to easily build up. The mucus build up decreases the amount of airflow to the alveoli which causes chronic coughing to force out the mucus with little to no success.

Figure A shows the location of the lungs and airways in the body. The inset image shows a detailed cross-section of the bronchioles and alveoli. Figure B shows lungs damaged by COPD. The inset image shows a detailed cross-section of the damaged bronchioles and alveolar walls.  Source: National Heart Lung and Blood institute, http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_WhatIs.html

What is NAC?

N-Acetyl Cysteine (NAC) is an antioxidant that facilitates creation of the body’s most powerful endogenous antioxidant—glutathione.  NAC was first thought to be a mucolytic agent—a dietary supplement that helps to break up mucus in the lungs—but has since undergone clinical trials investigating its role as a precursor anti-inflammatory molecule in the treatment of a variety of diseases such as cystic fibrosis, autism, chronic bronchitis, pulmonary fibrosis, and even schizophrenia.  NAC is available in many over-the-counter formulations, which are not required to be regulated under strict pharmaceutical standards as it should be.  Scientists warn that NAC, when not manufactured under airtight pharmaceutical standards is easily oxidized by air and becomes destabilized and thus rendered therapeutically ineffective.  The bad taste of NAC is the result of the sulfhydryl constituent in the amino acid cysteine.  When NAC is oxidized it releases very small quantities of hydrogen sulfide gas which may cause nausea in sensitive patients. What buyers should look for, then, is a pharmaceutical-grade NAC formulation that individually wraps each tablet instead of placing all of the tablets into one bottle (which repeatedly exposes the NAC to air with every pop of the lid).  As a second line of defense against further oxidation when being administered, the NAC of choice must have a buffered solution that maintains the pH of the solution in the acidic range.  This can be more commonly found in effervescent dosage forms of NAC. 

How does NAC work to alleviate symptoms of COPD?

When it comes to the cause and the progression of COPD, oxidative stress has been implicated as the primary culprit.  Typically with COPD this oxidative stress comes about when free radicals from cigarette smoke and environmental pollutants burden the lungs.  This oxidative stress and subsequent inflammation causes structural changes to take place within the lung tissues and airway walls, resulting in damage that is irreversible and breathing that is labored and difficult.

The COPD community can find relief as there is a significant and growing body of experimental and clinical research showing NAC’s strong antioxidative effect on COPD,¹ which means that for COPD sufferers, the progression of symptoms can be halted by supplementation of this glutathione prodrug. However, NAC conversion to glutathione is not able to repair the damage to those patients with emphysema, but can slow down further damage by reducing the inflammatory response around the lung tissue.  The same applies to chronic bronchitis; however NAC or the de-aceylated cysteine molecule is believed to have an anti-mucolytic effect that is able to alter the disulfide bridge linkages in the muco-globlin glycoprotein causing easier coughing up of mucus.

One study executed in Germany supplemented adults with acute bronchitis with 600 mg of NAC twice a day, and found that beyond reducing symptoms and improving patients’ quality of life, this nearly doubled the rate of bacterial eradication in the lungs compared to standard treatment.  In this same study, patients with COPD were able to improve performance on lung function tests by taking NAC—the observed improvement was even greater after exercise.²

Another study—this one in Israel—had half of the participating COPD patients take 600 mg of NAC twice a day for six weeks and followed by placebo for another six, and the other half took placebo for the first six weeks followed by NAC for the last six.  The researchers found that when the COPD patients in this study took NAC, they had improved lung function and exercise endurance, and were able to inhale and exhale more air.  Further investigation into these findings by the researchers led them to conclude that the overall improvement in lung function of these COPD patients is due to a reduction of “air trapping,” or a better transfer of air in the alveoli of the lungs.³

1. Dekhuijzen PN, van Beurden WJ. The role for N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(2):99-106.
2. Reichenberger F, Tamm M. N-acetylcystein in the therapy of chronic bronchitis. Pneumologie. 2002 Dec;56(12):793-7.
3. Stav D, Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest. 2009 Aug;136(2):381-6. Epub 2009 May 15.

N-acetylcysteine (NAC) is derived from the amino acid cysteine and is the precursor to the essential antioxidant glutathione.  NAC is  used to support a healthy immune system and good respiratory function. NAC is extremely well tolerated and safe.

Stress, fatigue and poor nutrition are all factors that can lead to a weak immune system . During the cold winter months our immune systems are compromised even more causing greater susceptibility to colds and flu.  In a study published by the Journal of Biochemical Pharmacology ^[1],  it was found that NAC  reduced the severity of the common flu  and inhibited the spread of it.  In another study it was found that long term treatment with NAC during the cold-season appeared to significantly reduce the frequency and severity of  the common flu in elderly subjects ^[2].

NAC may become oxidized when exposed to air specifically in open bottle of capsules. It is   important to protect  NAC from degradation and oxidation.  When NAC is oxidized it will not be able to produce glutathione, the antioxidant responsible for reducing inflammation in the respiratory tract.

A novel alternative to NAC capsules are effervescent tablets that dissolve and fizz when placed in water. Effervescent tablets provide an alternative for those who have difficulty swallowing capsules and allow for better and quicker absorption.  Solid capsules of NAC are dissolved gradually in the stomach and depending on the individual physiological factors capsules may not fully dissolve and cause irritation on the mucous membrane of the stomach. Effervescent tablets also allows for an even distribution of NAC.

The   common flu can cause   great discomfort  in the winter months.   Boosting your immune system with NAC  can  offer a source of protection against cold and flu during the cold winter months.  For more information, contact your Naturopathic Doctor.

References:

1. Geiler, Janina et al., N-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochemical Pharmacology, Volume 79, Issue 3, 1 February 2010, Pages 413-420

2. S De Flora, C Grassi, L Carati: Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J 1997, 10:1535-41.