Category: glutathione

PharmaNAC gets the thumbs up from Standford trial

Oxidative stress is defined as an excessive load of reactive oxygen species (ROS), which cause ongoing or reversible damage in the body. This can occur in individual cells, and in specific body organs, and can affect the health of patients at the whole body level.
Antioxidants can chemically react with ROS to quench and thus inactivate these reactive, damaging molecules. Cystic fibrosis is characterized by oxidative stress throughout the body and chronic inflammation in the lungs. Patients with CF are deficient in the body’s major anti-oxidant, glutathione (GSH). This is thought to be due to many reasons, including dietary insufficiency, but being the major anti-oxidant of the body, GSH is highly utilized in areas of oxidative stress and inflammation. GSH serves multiple functions and is utilized by cells to regulate physiological functions such as DNA transcription, RNA translation, and subsequent protein synthesis. It is utilized to regulate protein functions and is vital in regulating dietary absorption of nutrients, storage and availability of essential proteins and fatty acids.
Oxidation reactions are essential to fight infection and are generated when neutrophils ingest bacteria to rid the body of pathogens. For reasons still unclear, in CF, the environment in the airways is strongly pro-inflammatory. After neutrophils have been recruited, neutrophil-derived oxidants are released into the airways, and contribute to ongoing tissue destruction. Oxidants, which include hydrogen peroxide, hypochlorous acid, and other damaging particles called free radicals are released and create a vicious perpetual cycle of tissue destruction.

Continue reading “PharmaNAC gets the thumbs up from Standford trial”

Stanford University joins the GSH discussion

Screen Shot 2015-10-28 at 3.13.26 pmOnce upon a time there was a CF mother who was looking for anything that might help her son with CF. Sound familiar?

For those of you not familiar, Dr. Valerie Hudson’s foray into CF research began after her son, John, now 6, was diagnosed with cystic fibrosis as a baby. In her desperation, she taught herself anatomy from her older son’s high school anatomy textbook and began her long journey into the field of CF research. As the years passed, she became intrigued with the chemical glutathione and its role in the cell. After coming to believe that this chemical could make a difference in the health of her sons, Dr. Hudson eventually recruited Dr. Bishop to run a small, preliminary study using inhaled glutathione. Dr. Hudson presented their results.

Glutathione (GSH) is a tri-peptide, a very small protein, present throughout our bodies, but it appears in especially high concentrations in the epithelial lining fluid of the lungs.(Epithelial cells are the cells that line the inside of our lungs and they produce this fluid.) When the body has to deal with high levels of free radicals and oxidative stress, as is the case in CF lungs, the body provides higher levels of GSH to help it cope. GSH has several properties. It is a natural mucolytic. It helps regulate the immune response, as both an anti-inflammatory and as a cell-signaling molecule directing the white blood cells as to where and what to fight. It scavenges free radicals, and it is an anti-oxidant. Additionally, oxidized GSH protects proteins during stressful events in the lungs.

There is significant evidence of the importance of GSH in CF pathophysiology. At the 2000 CFRI Conference, you may have heard Dr. Rabin Tirouvanziam give an update on his GSH research. Dr. Bishop reported on a more recent study that showed that normal mice lung cells, when challenged with Pseudomonas aeruginosa, increase levels of epithelial lining fluid GSH six-fold to help fight the infection. By contrast, CF mice have significantly lower levels of a GSH response. This response is severely reduced in people with CF as well.

Dr. Bishop presented his small-scale, preliminary trial using inhaled glutathione. The GSH used was “pharmaceutical grade of 98.6 percent,” it was buffered and diluted to minimize irritation, and it was tested and found free of bacterial and fungal products. He also relied on the results from seven other published human trials, which observed no significant adverse events when used. In his randomized, placebo-controlled, double blind, clinical trial of inhaled GSH, Dr. Bishop recruited 19 subjects. Ten used the inhaled GSH and nine used the placebo. The age range of the subjects was from six to eighteen, and the trial occurred during the summer months. Patients inhaled through a mask nebulizer approximately 66 milligrams per kilogram of their body weight of GSH mixed with sterile water, divided into four daily inhalations sessions, each three to four hours apart.

The results of this clinical trial showed significant improvement in 11 out of 13 factors measured before and after use of GSH, including peak flow, overall improvement in health, and reduced cough. Dr. Bishop is the first to recognize the limitations of his trial (size is a significant factor), while drawing the following conclusions. GSH deficiency in epithelial lining fluid may play a major role in pathogenesis of CF, and GSH inhalation therapy appears to be effective for CF.

Dr. Bishop issued a clear caution to parents and adults with CF that further research still needs to be done before this can be considered a legitimate therapy for the CF community. Further research needs include a large, multi-centered clinical trial, the use of an FDA-approved product, and methods to increase convenience and control of administering the product. (Patients had to prepare their own solutions using capsules and sterile water, so doses were hand-prepared. This is time-consuming and dosages are not necessarily exact). Additionally, Dr. Bishop urged clarification of the route of delivery (oral vs.inhaled), dosage specifications, schedule of administration of the drug, patient selection, and other GSH augmentation tactics. Dr. Bishop warned that this is an experimental therapy not approved by the Cystic Fibrosis Foundation. No long-term studies have been done to ensure safety and efficacy of GSH use. He further cautioned his audience that the CFF recommends not using this GHS inhalation therapy until further studies are done.

The best pre-cursor on the market that is readily available as an oral dose seems to be NAC

  1. N-Acetyl-Cysteine (NAC)

It is derived from the amino acid L-Cysteine, and acts as a precursor of glutathione. NAC is quickly metabolized into glutathione once it enters the body. It has been proven in numerous scientific studies and clinical trials, to boost intracellular production of glutathione, and is approved by the FDA for treatment of accetaminophen overdose. Because of glutathione’s mucolytic action, NAC (brand name Mucomyst) is commonly used in the treatment of lung diseases like cystic fibrosis, bronchitis and asthma.

 When we asked around about this a few years ago it seemed that it was destined to remain a sideline alternative treatment – with the initial pilot research driven by a CF mother and a Dr Bishop out of a Utah in 2004. However, since then other research groups have been cautiously exploring the potential benefits. We know that the Royal  Children’s Hospital in Melbourne are now looking at it as part of a nutritional review and Standford University have just released a paper on it which I have posted below.

2015 Stanford University Paper: The role of NAC in producing GSH in CF patients

You can read about the original study here:  http://uvicf.org/researchnewsite/glutathionenewsite/protocol.htm

By the way if you’re keen, you can buy the oral cysteine “Fizzy NAC” online here: http://www.bioadvantex.com/us/catalogsearch/result/?q=fizzy+nac

 

Glutathione: What’s all the fuss about?

Glutathione is a very simple molecule that is produced naturally all the time in your body. It is a combination of three simple building blocks of protein or amino acids — cysteine, glycine and glutamine. The secret of its power is the sulfur (SH) chemical groups it contains. Sulfur is a sticky, smelly molecule. It acts like fly paper and all the bad things in the body stick onto it, including free radicals and toxins like mercury and other heavy metals. But that’s not all. Glutathione is also critical in helping your immune system do its job of fighting infections and preventing cancer. That’s why studies show that it can help in the treatment of AIDS and MS. It is critical for immune function and controlling inflammation. It is the master detoxifier and the body’s main antioxidant, protecting our cells and making our energy metabolism run well.

What’s glutathione got to do with CF?

Glutathione first seemed to come into the limelight relating to CF  in 1997 when Valerie Hudson worked with Dr Clark Bishop (CF Clinic in Salt Lake city Utah) to undertake the first trial using glutathione (GSH) to help her 2 young boys who both had CF. Its a great example of the fact that no one is more dedicated than the parents of a child with a chronic illness or disease.  You might like to check out the article here:
Article : A mothers fight against CF

In this issue of CHEST, Dr Bishop and colleagues report encouraging results from a small, double-blind, placebo-controlled clinical trial of inhaled glutathione in patients with cystic fibrosis. The rationale for this therapy lies in previous data reporting that glutathione levels in the lung epithelial lining fluid of patients with cystic fibrosis are low,1and that cystic fibrosis lung disease is associated with increased oxidative damage.2In addition, more recent studies36 have also demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR), which is defective in cystic fibrosis, regulates a substantial portion of glutathione efflux into the epithelial lining fluid.

The thinking has since shifted to N-acetylcysteine (precursor to gluathione synthesis) as a more effective way to support the body in generating gluathione on its own.

1] In 2006, stanford university started to investigate N-acetylcysteine for CF. – They did a small randomised placebo controlled, double blind efficacy study investigating NAC on lung inflammation in CF and two of the professors applied for a patent with regards to gluathione being used as a treatment for pulmonary lung disease.

Study # 1  

Study # 2

2] Standford university professors then trialled NAC for use with Autism (2012) as they believe it increases the capacity of the body’s main antioxidant network.

Study # 3  

Study # 4

The jury is out on whether glutathione is offering any real benefit but clearly there are lots of parents out there who are still trialling it as a supplement.

What about you? Have you tried glutathione with your child and can you guestimate as to whether its made any difference?