A new perspective on ethanol/aldehyde metabolisim and glutathione
Oh alcohol, the cause and solution to all of life’s problems. Mostly we’re worried about the problem the morning after, the nausea, headaches and other painful symptoms of a hangover.
When you browse the range of hangover mitigating supplements and drinks available on the market now, one of the most common ingredients is N-Acytyl-Cysteine, which delivers the amino acid Cysteine to the body primarily for glutathione synthesis.
Glutathione is the body’s master anti-oxidant and also a primary detoxifier of the cell, particularly in the liver binding (conjugating) which toxic metabolites in the the Phase 2 of the liver detox. In the liver Phase 1 enzymes break down compounds which think of as toxic, such as paracetamol and ethanol, into much more toxic by-products. It’s glutathione’s role to clean up these highly toxic metabolites.
Now here’s the conundrum, despite all the focus around supporting glutathione levels when you drink, we know that Acetaldehyde, the nasty ethanol metabolite, does not in fact react readily with glutathione (http://www.ncbi.nlm.nih.gov/pubmed/14574232). We know Aldehyde dehydrogenase 2 is the main enzyme breaking down the headachy acetaldehyde into the somewhat harmless acetate (which is oxidised into carbon dioxide).
Now this process of metabolising ethanol (and the tiny amounts of methanol) spews out lots of Reactive Oxygen Species, so having loads of glutathione around is definately good to keep those in check. But what about the Acetaldehyde?
I was looking at glutathione and alcohol, in particular sequestering aldehyde, and noticed a little connection I haven’t seen anyone explicitly connect the dots before in the hangover department. Drinkers/alcoholics have high levels of the enzyme Gamma-Glutamyl Transferase (GGT) (http://alcalc.oxfordjournals.org/content/40/6/511.full http://www.ncbi.nlm.nih.gov/pubmed/20150721). One function of this ezyme is breaking down Glutathione to Cysteinylglycine.
Then Cysteinylglycine rapidly sequesters acetaldehyde under physiologic conditions, (http://www.ncbi.nlm.nih.gov/pubmed/14574232 http://www.ncbi.nlm.nih.gov/pubmed/2867670 ) so this is another pathway the body has to process Acetaldehyde.
Alcoholics have elevated levels of GGT which can be used as a marker of how much they have been drinking. During oxidative stress, GGT gene expression is increased, and this is believed to constitute an adaptation to stress. How this happens is related to Nrf2, which is freaking cool and activates your DNA, but I’ll get back onto that in just one minute…
Supporting maximum glutathione levels it still important in any case as it goes far beyond alcohol damage and hangovers. The 100,000+ articles on PubMed.gov talking about glutathione (which incidientally is double what you’ll find searching for Vitamin C) correlate low levels of glutathione to over 74 major diseases. Despite the overwhelming scientific knowledge on glutathione, it’s had virtually no mainstream knowledge until just recently. And with what I’m about to show you, the tide is turning on glutathione awareness.
Interestingly the single most effective compound to deliver cysteine and raise glutathione was developed for alcoholics! (source)
After the Vietnam War, a high percentage of returning veterans were addicted to drugs and alcohol. Due to the controversy and unpopularity of the war, the veterans did not receive a glorious welcome and were ignored or shunned by most of society. Dr. Nagasawa’s own brother was one of the soldiers who suffered this fate. In response to this problem the Veteran’s Administration decided it needed better, more effective drugs than Antabuse to prevent alcohol abuse. They decided that they needed more new drugs that prevented alcoholics from developing fatty livers, which would lead to cirrhosis and eventually a liver transplant or death.
The team knew they needed compounds that were non-toxic to combine with cysteine in order to effectively deliver it to the cell. They realized that we do have such compounds in our own body, namely aldose monosaccharide, or the simple sugars produced when glucose is metabolized.
To test this possibility, grad student Jeanette Roberts [now the Dean of Pharmacy at the University of Wisconsin] prepared the sugar-cysteine condensation produced from 8 different aldose saccharides. The next experiment showed that livers that had an overdose of ACP [Acetaminophen, aka Paracetamol or Tylenol] plus the saccharide D-ribose combined with cysteine had 100% survival rate from the in vivo experiments, while the next best compound, glucose-cysteine did not perform nearly as well.
Eureka! Ribose-Cysteine protected the liver form a toxic dose of ACP. Ribose-Cysteine serves as an effective delivery method of bringing L-cysteine to cells, stimulates glutathione biosynthesis and protects them from toxins. The ribose-cysteine compound also makes for an ideal dietary supplement since it’s made from endogenous elements already in our body.
Further experiments went on to show that ribose-cysteine was even more effective [~300%] than NAC [N-Acetyl-Cysteine] in increasing glutathione content within a liver cell.
Dr Herbert Nagasawa is one of the world leading researchers on glutathione and medicinal chemistry. You may remember the Anthrax scares after the 9/11 attacks. The US Department of Defense put out a call to the scientific community to develop a much faster acting cyanide antidote to meet their “three minute standard”. The existing one took up to half an hour to take effect, which is a long time to pray when cyanide can cause brain damage and death in only 5 minutes. Herb was the scientist who created the new antidote which worked in 3 minutes, proving otherwise to those who thought it was impossible.
Similarly for cysteine delivery and glutathione synthesis, Herb was the man`who again achieved the impossible and smashed through the glass ceiling in glutathione support with the RiboCeine compound, which also conveniently supplies Ribose for ATP (energy) production. The National Institutes of Health (NIH), The Veteran’s Administration Department of Medicine and other scientific institutions have funded, peer-reviewed and published twenty studies over the last 25 years demonstrating the unsurpassed effectiveness of RiboCeine™ in glutathione enhancement and cellular protection.
When it we drink alcohol we want more glutathione to take care of the free radicals and more GGT to break it down to Cysteinylglycine that will sequester the nasty acetaldehyde.
So how do we get more Glutathione and Cysteinylglycine? The two key factors are the availability of the amino acid Cysteine in the cell and the activation of Nrf2 signalling pathway. Nrf2 is a primary cellular protective mechanism in the body. It’s activated by oxidative stress and toxins, and the end results is the transcription of about 200 genes in your DNA which encode and create a whole raft of protective enzymes and proteins, including:
- Glutamate Cysteine Ligase (GCL) which performs the rate-limiting step in the synthesis of glutathione
- Glutathione Peroxidase (GPx), which is required for glutathione to neutralize powerful damaging free radicals such as Hydrogen Peroxide
- Gamma-Glutamyl Transferase (GGT) which maintains glutathione homeostasis (balance) and breaks down glutathione to Cysteinylglycine, which binds to acetaldehyde.
Now all those vices, like boozing, activate Nrf2 from the oxidative stress as a reactive defensive response. What if we could proactively supply Cysteine and safely activate Nrf2, boosting our glutathione, GPx and GGT levels?
Only recently science has been uncovering the unique properties of some specific plant compounds, in particular curcumin from turmeric and sulforaphane from broccoli sprouts. These compounds are potent Nrf2 activators and are thought to be responsible for some of the enhanced health benefits of these vegetables and spices such as inhibiting cancer.
Silymarin is found in the Cordyceps mushroom which is held in high regard in Chinese medicine and is known to support liver function, and you can never have enough good liver support when hitting the booze.
Other compounds which help protect against alcohol damage are Quercetin, Selenium (which is required for the glutathione peroxidase enzyme) and Resveratrol (the molecule found in the skin of red grapes which has some time in the media spotlight for it antioxidant and anti-aging properties). Vitamin C and Alpha-Lipoic acid are scientifically validated for their essential roles as anti-oxdants and working hand-in-hand with glutathione.
Ok, so you want the ultimate drinking companion, but do you want the hassle of buying a dozen different supplements and scoffing a dozen different pills and capsules each time you enjoy a few (or more) drinks?
The good news is there is a product which contains all these ingredients, and it’s only one on the market sporting the patented RiboCeine compound, which is by far the most effective glutathione enhancer. The supplement is called Cellgevity.
Whether my hypothesis of this acetaldeyhde metabolism is actually how it goes down on the cellular level, and what percentage of acetaldehyde would be metabolised via with pathway, I’ll have to leave to someone with a PhD and a laboratory.
One thing I can tell you for certain is this; Myself, other friends and acquaintances who’ve been taking it have all noticed the beneficial results after a big night out on the town. While my motivation levels can be low the next day, partly from the lack of sleep, I haven’t had the kind of sickly hangover where you want to go into a coma until it passes for a looong time.
Now I almost feel bad telling you this is the ultimate drinking/hangover supplement. I spread the word on Cellgevity to promote health, not how to get away with boozing more! But hey, we’re going to drink what we’re going to drink, so we may as well have the best protection possible.
Personally I take it religiously every day, as you might a multi-vitamin, as it’s the premier anti-aging supplement. Then I double up the dosage on the days I’m having some drinks for the extra protection.
Before you think this is some random out-there supplement, I’ll share a tiny list of some of the people who use Cellgevity regularly in their quest for optimal health and performance:
- Greg Norman, former world #1 golfer for 6 years
- Evander Hollyfield – 5 times world heavyweight champion boxer
- Chris Mullin – NBA Hall of Fame
- Dr Don Colbert – NY Times best selling health author
- Dr Douglas Harringon – former member of the Stanford heart transplant team
Now there’s only one thing left for you to do, which is get a bottle of Cellgevity for yourself and see what it does.
There’s an option if you order it for 3 months you get a significant discount. The company offers a 30-day no-questions money back guarantee. On top of that I’ll add my own personal guarantee. Give the Cellgevity a proper go for 2-3 months and if you don’t get any results and aren’t interested in using it further I’ll PayPal you the commissions I earn when you order through my link here.