Welove to unwind on weekends with a nice cocktail at a bar somewhere.
I’m an alcohol lightweight with an easy tendency to develop Asian flush, hence my go-to cocktail is a “weak” aperol spritz. To be honest, I’m more interested in getting a nice Instagram shot than what is actually inside the drink.
Of course, though, there are many other factors that can influence how much alcohol we do actually consume. Work stress, for instance. The stress of dealing with this COVID-19 pandemic, for instance. Having peers who drink heavily and frequently can also influence us to drink more than we ought to.
Drinking isn’t exactly the main problem — it’s what happens as the alcohol gets metabolised by the liver prior to excretion.
The biochemistry of alcohol metabolism
The cells in our liver take 2 steps to metabolise ethanol (alcohol) into acetate (vinegar).
1. Initially, the alcohol dehydrogenase (ADH) enzyme converts ethanol into acetaldehyde.
2. The acetaldehyde dehydrogenase (ALDH) enzyme then converts acetaldehyde into acetate.
Both these reactions are oxidation reactions, where electrons are removed from the ethanol (Step 1) and acetaldehyde (Step 2). These electrons are transferred to nicotinamide adenine dinucleotide (NAD+), which then reduces NAD+ down to its reduced state of NADH.
Unfortunately, the rate of Step 2 activity tends to be slower than the rate of Step 1, hence when one drinks alcohol in excessive amounts, their faces tend to go red, they get nauseous, and they get dizzy. Those are symptoms of acetaldehyde toxicity right there. Therefore, Asian flush is also a symptom of excess acetaldehyde in the blood.
Why do we call it Asian flush though? This article mentions that:
Due to genomic differences, 80 per cent of Asians have an overactive alcohol dehydrogenase. Hence, they break down alcohol into acetaldehyde very quickly — even up to 100 times quicker. Since alcohol is broken down faster, this is why you might experience little to no alcohol “buzz”.
On the other hand, most Asians have an inactive variant of the second before-mentioned liver enzyme ALDH2. This means that the by-product acetaldehyde takes a much longer to clear from their blood.
What happens when we have too much acetaldehyde in the blood?
Of course, as acetaldehyde is a reactive aldehyde and contains those reactive carbonyl groups…
These reactive carbonyl groups can react with other biomolecules in our body, such as proteins. That’s basically how excess glucose in our blood can react with haemoglobin proteins to give off a HbA1c blood reading that diabetics dislike — we’d be looking at an aldehyde-amine reaction.
These reactive carbonyls can also react with cellular DNA to force mutations and potentially cause cancer, because DNA strands also have free amine groups that can react with these carbonyls now.
It is important to note that we don’t get cancer from one night of binge drinking. We are at higher risks of developing it, however, if the drinking was sustained chronically over a long period of time.
This is essentially why alcoholics are at greater risk of developing liver cancer.
Their liver has to metabolise all the alcohol that they are consuming. If they drink themselves drunk on a regular basis, there will be constant periods of time when their blood acetaldehyde levels are higher than normal, which then has a higher propensity to cause greater amounts of damage to their liver cells. As more damage is sustained to the liver, the probability of developing liver cancer/health complications would then be much greater, no?
Unless, of course…
One has a good defensive mechanism against all that acetaldehyde.
Our liver cells contain the antioxidant glutathione (GSH), which can also be used for acetaldehyde neutralisation. So yes, we do have a defensive scheme against acetaldehyde toxicity, and that comes in the form of glutathione, which is regulated by the nuclear respiratory factor 2 (nrf2) pathway:
The nrf2 pathway therefore regulates the cell’s internal production of GSH antioxidants. GSH is able to neutralise the pro-oxidants that are formed from aerobic respiration, disease or exposure to toxins, and in doing so, can aid in delaying the onset of oxidative stress in the body — provided that the rate of GSH production is sufficient to counter the rate of pro-oxidant formation.
Two molecules of GSH can accept electrons and be oxidised into a single molecule of oxidised glutathione (which we term as GSSG). GSSG can be reduced back into GSH within the cell via the activity of the glutathione reductase (GR) enzyme. Hence, these 2 molecules of GSH can be constantly cycled back and forth between their reduced GSH and their oxidised GSSG states, and deal with the transfer of hundreds of electrons.
This continuous GSH cycling allows for the neutralisation of many ROS molecules over the cell’s lifespan. In comparison, dietary antioxidants such as Vitamin C (ascorbic acid) can only deal with the transfer of 2 electrons (where it gets oxidised into dehydroascorbic acid)… unless there is adequate GSH to deal with the regeneration of Vitamin C back into its reduced ascorbic acid form. However, while GSH can reduce dehydroascorbic acid, ascorbic acid cannot reduce GSSG, because their redox potentials are different. Hence, we cannot rely on Vitamin C to regenerate GSH, but alpha lipoic acid can do so.
Therefore, the production of GSH internally trumps the consumption of Vitamin C.
GSH production counters ROS activity. Vitamin C production also counters ROS activity. However, as GSH is able to regenerate Vitamin C but not the other way round, I’d say that GSH production is more useful than Vitamin C consumption, wouldn’t you think? Especially when it comes down to supporting our immune system against infections?
But the problem is that we all have different cells that are endowed (genetically) to produce glutathione at different rates. If the glutathione that we do produce is able to keep up with the detoxification load, then we’d be in good shape.
If, however, it doesn’t…
We lament that life is unfair and wonder why that guy who smoked 3 packs of cigarettes a day can live for so long without any lung cancer issues, while someone else is born with cancer right away?
It all depends on what we’re born with. Now that’s genetic.
We’re looking at the prowess of one’s defensive mechanisms.
That’s why not all smokers will get lung cancer, and neither will all alcoholics get liver cancer.
The risks for them are higher, but if their defensive mechanisms have enough juice in them to neutralise the initial stages of the problem… It would be more difficult for them to get it. Everyone is born with cells that utilise the nrf2 pathway to produce glutathione. But the rate of GSH production will vary from person to person. If the baseline rates were able to neutralise the threats, then the threats wouldn’t be much of a threat at all.
However, as GSH is a key player in regulating Vitamin C regeneration (and therefore a major player in one’s immune health), then it would be easy to correlate a weaker immunity with lower GSH levels.
It all has to do with the defensive mechanisms that our body possesses.
Genetically, some people will have a higher tolerance for alcohol because their liver cells are able to produce more ALDH2 to cope with a higher alcohol load. Some people may age slower because their cells are genetically equipped to produce more glutathione.
However, one thing is for sure.
The lifestyle ways that we subscribe to are partially responsible for the toxic loads that we have to deal with. We do know that excess stress can be quite damaging for the body, for instance.
And we don’t want to give a cancer patient extra stress because it could worsen their condition.
Unfortunately, we may not necessarily feel the effects of poor lifestyle choices that immediately. As the saying goes,
It only takes a spark to get a fire going.
But when it rains, it pours…
And that can be so much more damaging to our health.
It’s not just about the alcohol that we consume; it’s also about how well our body actually detoxifies and processes it.
Unfortunately, nobody really stops to think about properly maintaining the body’s detoxification processes, right?
We do know that it is necessary for shutting down production plant equipment every now and then to conduct maintenance on that equipment to keep it in tip top condition. Why aren’t we doing it to ourselves better, then?
It can be pretty expensive to go to a healthcare facility and not be able to obtain a proper solution to one’s health problem, isn’t it? Wouldn’t prevention be a better option instead?
For proper liver support and detoxification, do have a look at What Nutrients Support Digestion And Detox In Our Body?
This article was originally published in Vocal.
Joel Yong, PhD, is a biochemical engineer/scientist, an educator and a writer. He has authored 4 ebooks (available on Amazon.com in Kindle format) and co-authored 6 journal articles in internationally peer-reviewed scientific journals. His main focus is on finding out the fundamentals of biochemical mechanisms in the body that the doctors don’t educate the lay people about, and will then proceed to deconstruct them for your understanding — as an educator should.