What’s Your Poison?

(Shameless wine drinking boomerang from New Years. Press play to watch me cheers you over and over again. Or don’t. It’s fine. I’m lame, It’s ok.)

The inspiration for this particular post came in the form of an incredibly nasty hangover. One of those head spinning, stomach curdling, moan-out-loud-and-beg-for-death kind of hangovers. As I rapidly approach the end of my twenties, with my thirties standing in a robe holding a scythe on the horizon, hangovers are no walk in the park. But maybe it’s just me, since this particular hangover occurred after one of my good mates came back from a holiday trip to his family home in the UK. He’s in his forties, a horrible influence with a pint in one hand and a glass of bourbon in the other and was probably able to walk with a spring in his step, whistling some Mary Poppins song the next day.  Meanwhile, I was struggling to pull myself together with crackers and a glass of water.

So, what is the biology behind alcohol?

We all know the effects alcohol has on our fragile little bodies. A nice spreading warmth and delusional bold feeling that comes with the flow of liquid courage.  This followed by some slurring of our speech (Dysarthria) and the tell-tale weeble-wobble (Ataxia), some nausea and maybe vomiting followed by the eventually slip into blissful unconsciousness. Ah, lovely.

But let’s take a look at some of the biological implications of alcohol consumption

The Gastrointestinal Tract

Alcohol is absorbed into your blood stream rapidly through your stomach and intestinal lining. It burns through your mucosal cells with a fiery vengeance. The nausea and vomiting that generally follow a night of making it rain ethanol down your gullet is from inflammation of the stomach lining.

Bad news. Chronic, heavy alcohol consumption can lead to malabsorption and vitamin deficiencies, which may lead to some terrifying effects. Thiamine is the vitamin that takes a substantial hit when alcohol consumption becomes heavy and chronic. Thiamine is a wonderful little molecule called a coenzyme – it is needed for proper cell functions to occur. It plays a big role in carbohydrate metabolism (getting sugar broken down to feed your hungry cells), neurotransmitter synthesis (helps make those happy little brain chemicals) and even in the building blocks of our DNA (nucleic acids).

Our brains, in particular, take the hardest hit from alcohol – both in the acute effects of short term use and the long-term effects of thiamine deficiency in the form of Wernicke-Korsakoff syndrome.

So, let’s travel on up from the gut to the brain and see what goes on when we throw back a few.

The Brain

The Brain, swishing around in a cozy little hot tub of cerebral spinal fluid in the iron fortress of the skull, is seemingly protected from the outside world. And it is– to an extent. Like a large blow to the head can cause a nasty effect on the brain, so too can some of the things we ingest. Alcohol has the ability only a few molecules have — it can pass through the blood brain barrier (the BBB). The BBB is a collection of densely packed cells that prevent the passage of many harmful substances into the brain’s circulatory system.  Alcohol happens to be the right size and shape to slip past the guards at the gate and wreak havoc inside the gooey tissue.

The Cerebellum (which adorably translates into “little brain”) is a wrinkly little structure at the back of our brain near our spinal cord. Its main job is to keep a tight regulation of our voluntary movements including posture, balance and coordination. Your slurred speech is also a direct result of alcohol’s unforgiving assault on your adorable “little brain.”

What about that booming headache the next morning? Well, it is a few parts dehydration and a few parts angry pain receptors that dot the meninges – the layers of tissue that cover your brain. Alcohol appears to be toxic to these protective coverings and the next day they are reeling from the effects.

And that is just the acute effects of alcohol consumption. Abusive alcohol use can do some very serious damage to your ooey-gooey center.  Remember the thiamine deficiency that occurs with chronic over use? The lack of thiamine really messes with your neurons and glial cells. A deficiency eventually leads to damage in areas of the brain, triggering apoptosis (a fun word that means programed cell death. Okay, it is actually Greek for “falling off” but it’s really a process that your cells undergo as they die. All cells are destined to do it but sometimes they are bullied into it). All this neuronal damage leads to an interesting pair of disorders.

So, let’s pour a pint and have a chat about Wernicke-Korsakoff syndrome

IMG_20171219_184306_363

Two Guys Walk into a Bar

Wernicke’s encephalopathy (fancy word for “something is wrong with your brain.” Seriously.) and Korsakoff Syndrome are two different disease states but they often go hand-in-hand so neurologists frequently lump the two together.

Wernicke’s encephalopathy is characterized by:

  • Confusion or a change in mental state
  • Some pretty noticeable changes in the eyes, including Nystagmus – involuntary rapid eye movements (Check out a video of it HERE!)
  • Difficulty with walking and balance – otherwise known as Ataxia

The presence of at least one of these symptoms, coupled with being thiamine deficient, usually points to Wernicke’s. With increasing apoptosis and accumulating neurological damage, the encephalopathy often gives way to Korsakoff syndrome.

Korsakoff Syndrome is all about your memories. Or lack there of. The syndrome incudes amnesia (or memory loss) in both the anterograde (memories that come after or “new memories”) and retrograde forms (memories that happened before the onset — sometimes extending years into the past).

An interesting feature of Korsakoff is the ability of the person affected with the syndrome to try and compensate for their deficits. They often engage in something called confabulation – they lie without any intent to deceive. The afflicted will come up with fabricated or imaginary experiences in order to fill in all the memory gaps.

So now that we have explored the gut and the brain let’s zoom into what alcohol does to our DNA.

Yeah, drink up, it gets worse.

Our DNA

There is a recent study that popped up on a popular Facebook page (that has something to do with passionately loving science) that shows alcohol’s damaging effects to haematopoietic stem cells – or the cells that renew our blood. Accumulation of damage can lead to a horrible cascade that eventual leads to mutations and quite possibly, the C word.  The study specifically looked at damage caused by acetaldehyde.

Acetaldehyde is the by product of alcohol metabolism.  There is a multistep process that our body undertakes in order to rid ourselves of the alcohol we have ingested.

First – an enzyme called alcohol dehydrogenase breaks down ethanol (our friend alcohol) into acetaldehyde, which is toxic to our body – as the evidence suggests. Then another little enzyme called aldehyde dehydrogenase 2 (ALDH2) breaks down the nasty metabolite into something that won’t poison us.

The unfortunate news is that some people have a defective ALDH2 enzyme and acetaldehyde builds up rapidly in their body. More unfortunate news, enzymes get saturated. This means that there may be too much acetaldehyde and the enzyme just can’t work fast enough to remove it from our system.

From the mouse model, the evidence suggests that aldehydes can do some nasty things to DNA, including DNA protein cross linking, which can damage chromosomes. This chromosomal damage can cause some funky chromosomal rearrangements when cells undergo division, which would eventually lead to malignancies (fancy word for cancer).

On Prophecies of Doom

Now before we vow to never drink again, much like the ritual that follows a hangover, the study had a fairly narrow scope. First, the focus was on a specific disease called Fanconi anemia, a rare disease caused by unrepaired DNA mutation. They looked specifically at acetaldehyde’s role because many of those afflicted with Fanconi anemia have a defective ALDH2 enzyme, namely Japanese Fanconi patients. The hallmark of Fanconi anemia is the failure of specific DNA repair mechanisms, which leave mutations unchecked, leading to blood disorders and eventually specific cancers.

Acetaldehyde still appears to have the ability to crosslink DNA and really screw it up, but the good news is that most of us have a working mechanism for fixing these DNA mutations.  Specifically, a repair protein called FANCD2, that is directly defective in the case of Fanconi anemia patients. Loosely meaning, we can repair the damage acetaldehyde may do to our haematopoietic stem cells.

The researchers argue that it does illustrate that acetaldehyde can damage our DNA which may explain the epidemiological link between alcohol and cancer risk; however, this study, frankly, is not very relevant to the general consumer of alcohol.

Can alcohol cause cancer? Sure it could, what doesn’t?

Can it damage your brain? You bet your ass it can.

Can it make you dance? No, absolutely not.

So, drink up friends and enjoy that pint of beer or glass of bourbon, but for the love of God put down that tequila shot … even if it is free.

20171201_164914

Cheers!

 

___________________________________________________________________________

Images: Erin Matthews

Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Garayocechea et al. Nature. 2017
The role of thiamine deficiency in alcohol brain disease. Martin et al. NIH. 2004
Effects of ethanol on the cerebellum: advances and prospects. Luo. 2015
The effects of alcohol consumption upon the gastrointestinal tract. Bujanda. 2000

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s