Startling Science Behind Alcohol Biochemistry Plus a Supplement StrategyDec 13, 2021
By Doc Mok
Whether it be celebration, mourning, or stress management, alcohol is at the center of our times of emotion. I am a gastroenterology or a GI doctor. A large part of my clinical practice and study involves liver and pancreas diseases. Both of these organs are affected by the science behind alcohol.
The Reason Why I Decided to Make a Change, Based Upon the Science Behind Alcohol
It was the fall of my first year being an attending (full-fledged doc) when I was performing a routine procedure on a sick patient. During that procedure, my patient arrested, and though we got them back, he later died. I am not a family member to the patient, but as healthcare providers, we feel our patients’ direct loss. Call me sensitive, but my patient’s loss made me lose sleep, feel anxious, and question my judgment.
My system revved up, and to calm it down, I would come home from work and have one alcoholic beverage. Though I was not an alcoholic, I realized that the science behind alcohol was why I was in more need of a drink to calm my nerves.
Over time, I realized that this was merely placing a Band-Aid on the underlying sympathetic nervous system imbalance that I was experiencing. So, like an excellent nerdy doctor, after some reading on the science behind alcohol, I came up with a plan to self-experiment and cut alcohol out of my life for 30 days.
Within weeks I was sleeping like a high school student again. I was killing it in the gym and lifting 10% more than the weeks prior. My body fat dropped by 5%, and I just felt happier. As discussed before in our articles on the science behind alcohol (click HRE for Drink that Science), Sleep and Alcohol (HERE), and Drinking and Maximal Being (click HERE), alcohol has long-lasting effects on your body.
Therefore, this week I thought I would read and nerd out on how alcohol metabolizes and the effects of alcohol in the cell on your body, and the science behind alcohol.
Alcohol Statistics Past and Present
Sales have risen to near 30% during our present pandemic, resulting in more admissions to the hospital for an alcohol-related illness. Furthermore, about one-third of people stated they are drinking more now than before.
Over the last decade, 88,000 have died as a result of alcohol. There has been a relative doubling of alcohol-related deaths from 1999 until the most recent figures. In the United States, mortality due to all alcohol-related liver diseases is 5.5 per 100,000. Estimates are higher in 25-35 and Veterans. Worldwide about this mortality rises to 10%.
Alcohol Also Causes Cancer and Causes Chronic Illness
Drinking alcohol also raises the risk of certain cancers. Namely of the head, neck, throat, larynx (voicebox), esophagus, colon, rectum, liver, and breast. This risk also rises. The more your drink and falls, the less you drink.
As if that wasn’t enough, alcohol interferes with sleep, your body composition, and your mood. Alcohol use can directly lead to chronic liver failure, diseases of the pancreas, and the gut. Alcohol can interfere with your heart’s pumping ability and muscle structure, termed dilated cardiomyopathy.
The Science Behind Alcohol Absorption
About 20% of alcohol is absorbed in the stomach and the remainder in the small bowel. As a result, alcohol will considerably shift your microbiome and poke holes in your intestinal lining, leading to leaky gut syndrome.
95-98% of alcohol metabolizes via the liver. So, two enzymes are indicative of the effect of alcohol on this organ.
- GGT is an enzyme found in the cell membranes of several body tissues, including the liver and spleen
- Carbohydrate‐deficient transferrin (CDT) generates as a result of alcohol inhibition of transferrin glycosylation.
The remainder of your alcohol (under 1%) eliminates in breath, sweat, and urine. To properly digest your alcohol, your body uses:
- Uridine diphosphoglucuronate–glucuronosyltransferase (UDP)
- UDP–sulfotransferase, producing ethyl glucuronide and ethyl sulfate
When you cannot get rid of or metabolize alcohol, toxic byproducts can build up in the cell and damage your cells’ contents and the organs for which your cells compose. Therefore, it is essential to consider removing or eliminating alcohol for at least a little bit.
An overview of your cellular structure
To summarize what occurs in your cells, let me first go through your cell’s basic structure. The section is like a water balloon. It has a porous outer lining termed a membrane. This membrane is made mostly of fats. The water balloon is cellular structures called organelles.
These organelles perform essential jobs like the mitochondria make ATP or energy; your endoplasmic reticulum helps detoxify your body. Your peroxisome also helps with making the balloon lining. Many of these organelles are involved with an impact on the science behind alcohol.
How Alcohol Can Affect Your Cell
After it is absorbed in the stomach, alcohol breaks down via an enzyme termed alcohol dehydrogenase (DH). This enzyme converts alcohol to a highly toxic compound, acetaldehyde using NAD in cells water space (the cytosol) that wreaks havoc. We will come back to acetaldehyde.
The alcohol breakdown process can also occur via the peroxisome and microsome or smooth endoplasmic reticulum [microsomal ethanol-oxidizing system (MEOS)]. The microsome uses cytochrome enzymes 2E1 in microsome via NADPH to NADP + 2 water to break down alcohol. Catalase uses in the peroxisome.
Next, acetaldehyde, a highly toxic substance, is turned into acetic acid (yup, it is a ketone) in the mitochondria by acetaldehyde dehydrogenase again using NAD. Acetic acid, a ketone, is easily removed from the body via the means stated above (urine, sweat, etc.).
When Alcohol Dehydrogenase Saturates, Damage Occurs
The problem arises when your alcohol DH enzyme gets saturated quickly. This digestion leads to a build-up of toxic substances. As a result, your NADH level raises, leading to redox reaction, and that can damage many organs, including:
- The organelles
- The brain
- The liver
- The heart
- DNA to form carcinogenic DNA adducts such as 1,N2-propanodeoxyguanosine
Due to this widespread collateral damage, it is important to limit intake. Limiting your intake will allow our body to break alcohol down and eliminate toxic byproducts, preventing damage to the above. If you drink to excess, the system becomes overwhelmed, and the consequences are numerous.
The Long-Lasting Effects of Alcohol Science on the Brain
Phosphatidylethanol (PEth) is a phospholipid formed by phosphatidylcholine reaction with ethanol catalyzed by phospholipase D in the red blood cell membrane.
Red cells get a free pass through a brain defense wall called the blood-brain barrier. Not only does alcohol poke holes in this barrier by a process called lipid peroxidation, but PEth can pass directly through by riding on your red cells.
PEth does not appear to be influenced by age, body mass index (BMI), sex, kidney disease, or liver disease. What is most scary is that PEth has a half‐life of approximately 10‐14 days, although this can be longer with more chronic, repeated heavy alcohol consumption.
This biochemistry means that PEth will stick around in your system for two weeks after even one drink. It is due to PEth that I recommend stopping drinking for at least two weeks to gauge how you feel correctly. Allowing two weeks minimum will lead to eliminating the psychoactive substance and improving your mood and sleep.
Other Nervous System Effect from The Science Behind Alcohol
As if that was not enough of an effect on your nervous system, alcohol also acts on other parts of your neurochemistry. The GABA is a system in your body that can dampen awareness and alertness. It will lead to the relaxation of your muscles and you. Using this system is how benzodiazepines like Xanax, Ativan, etc. work, allowing calming effects and, in high doses, lack of awareness of stupor (blacking out). A trade-off of this sedating effect is rebound hyperawareness and low quality in deep, restful sleep.
The role of glutamate in your body is to alter your brain cells (neurons). Alcohol changes this signaling, which is a reason why your coordination is off when you drink. It is also why people fall when they have been drinking too much. Finally, feeling depressed, anxious after imbibing alcohol can often be due to the variable effects of alcohol on your neurohormones.
The effects of the science behind alcohol are also due to the formation of secondary substances that can gunk up your brain’s jobs. Alcohol can also
- Form Salsolinol = adducts with the brain signaling chemical dopamine, which may contribute to alcohol dependence
- Acetoald + dopamine also forms Tetrahydropapaveroline = which makes endogenous morphine.
- Isoquinoline or carboline compounds = that displace neurotransmitters
- Decreases cytochrome c oxidase (COX) activity = central to a variety of neurodegenerative illnesses, such as Parkinson disease and Alzheimer disease (AD)
Summary of the effects of Alcohol Science on your Neurological System
- GABA – what decreases awareness and increases relaxation of mentation and muscles
- Blocks glutamate binding to NDMA (N-methyl-D-Aspartate) to reduce sodium and calcium-dependent neurochemical signaling – slowing signaling.
- Directly inhibits the release of neurotransmitters, such as serotonin, acetylcholine, dopamine, noradrenaline, endorphin, encephalin, and neuropeptide Y
How Alcohol Can Damage the Heart
If you have ever felt short of breath or had your heart racing after a holiday binge event, the term holiday heart may apply. What happens is that over time, your heart muscles will weaken and remodel as a result of alcohol damage. This disease state is called dilated cardiomyopathy or sometimes cardiomegaly.
Cardiomegaly results from fat deposits via above (lipid perox, apoptosis, WBC infiltration, mitochondria damage, low respiration, low energy). You, therefore, get a heart with a weak muscle and a large cavity. Consequently, you can fill the heart with more blood but cannot pump it as well. Such changes lead to changes in your heart’s ability to get fluid out of the tissue and change your heart’s electrical system, leading to arrhythmias.
On the flip side, alcohol has some polyphenols that fight DNA-damaging reactive oxygen species (ROS). Such compounds include quercetin, catechin, tannic acids, and resveratrol, which has the following benefits:
- Reduce atherosclerosis
- Lower LDL
- Inhibit platelet-derived growth factor
- Anti-inflammation, ischemia
- Lowers hypertrophy response
- Lowers fibrosis
The effects of alcohol on the GI tract
Over the last several months, there has been an extraordinary number of alcohol-related Gi cases in the hospital. Alcohol can damage your small bowel and cause leaky gut and damage your liver, pancreas, and stomach.
The way alcohol can affect the stomach and small bowel directly damages the mucous barrier and the epithelium. Alcohol kills some of your microbiome, which, as written in our microbiome Articles (Microbiome 101 HERE and Transbiosis HERE), has numerous effects. Finally, in the stomach, alcohol also causes a low acid level due to the drop out of parietal cells, which can cause heartburn and reflux and impair protein digestion.
When acetaldehyde builds up in the liver, the fatty acid biosynthesis rates, and subsequent esterification into triglycerols increase. The result is an increased fat deposit both within the liver and outside of the liver on your tummy. Next, your protective scavengers, the Kupfer cells, release profibrotic substances, and inflammatory compounds leading to hepatitis and cirrhosis. You also get depletion of energy, causing apoptosis (cell death) and liver failure. Click HERE to learn more about fatty liver disease and HERE on how to Detoxify the Liver HERE.
The Science Behind Alcohol Absorption Supplements
As stated above, however, alcohol is not all doom and gloom. There are means for combatting the effects of alcohol on your body, and there are also things that you can take to mitigate the effects of alcohol. That said, I want to lend perspective. If you need to take many supplements to prevent bodily damage, shouldn’t you moderate or avoid it in the first place? Let’s proceed.
Activated charcoal will help bind up alcohol and prevent the stomach and small bowel absorption, as above. There are few harms in taking charcoal, but 2-3 caps before each alcoholic drink—Chase with adequate amounts of water. Also, ensuring you have hydrated properly and eaten before imbibing will help prevent alcohol absorption and reduce the effects.
As an interesting anecdote, I have found in the past that a casein protein shakes before bedtime assists with limiting the effects of alcohol, likely through absorption. This sentiment has yet to be formally studied. However, the slow absorption, I suspect, leads to a low level of mucosal protection delaying the alcohol absorption rate.
Supplement with Alcohol Substances? Resveratrol
As discussed above, resveratrol, found in red wine, has many potentially beneficial effects on alcohol science. Specific substances found in resveratrol supplements include piceatannol or the seeds of Euphorbia lagascae, which protect your heart from alcohol.
Another substance is citrocard or phenibut citrate, which scavenges free radicles > increased ox phosph. The question is, at what point do these excellent effects outweigh the toxic effects of alcohol itself. Generally, with one drink, it is enough to balance the impact of alcohol with the trade-off of the effects on body composition, sleep, mood, etc. To gain the benefits of these compounds without the effects of alcohol, take supplemental resveratrol 100 mg daily.
Protect Your Cells Using the Science Behind Alcohol Supplements
Numerous studies highlighted that curcumin (turmeric) is a potent scavenger of various compounds produced by alcohol. By this I mean, ROS, such as superoxide anion, hydroxyl radicals, and nitric oxide. You can cook with it or use it as a supplemental pill in 500 mg daily dosing.
Another protecting compound is IL-6 that prevents apoptosis and oxidative stress in mitochondrion caused by alcohol. IL-6 is a drug via infusion and is not available for pill-form consumption at this time. Pyrroloquinoline Quinone (PQQ) is a powerful anti-oxidant. PQQ can also prevent the generation of reactive oxygen species in manners more potent than vitamin E and C. You can take this before drinking alcohol
Betaine HCL is a substance that can decrease lipid peroxidation and prevent apoptosis. This aids in low acid states and damage to parietal cells caused by alcohol. If you feel worse with this, you likely do not need it and could indicate acid reflux disease. Do not take this if you have stomach issues, are on a PPI (like Nexium, Prilosec, Protonix, etc.), or have prior ulcer disease. Please consult with your physician first.
s-adenosyl-L-methionine (SAMe) generates glutathione and can preserve mitochondria and phosphatidylcholine synthesis. Taking this with alcohol can improve the effects of alcohol on your cellular structure theoretically. I will say that liver literature is mixed regarding this therapy. Another consideration is that SAMe can lead to DNA methylation, which silences genes (sometimes good and sometimes bad).
Histamine, Sulfites Can Worsen the Science Behind Alcohol
If this supplement does not help or makes you feel worse (itching, flushing, red face, funny or bloody nose, eczema, psoriasis, insomnia, migraines), blame histamine. Histamine sensitivity is usually from the following genes.
- DAO (D-Amino Acid Oxidase)
- MTHFR (methylenetetrahydrofolate reductase)
- MAOA (Monoamine oxidase A)
Therefore, I would recommend taking nettle leaves, quercetin, bitter orange fruit, or bromelain.
The next effect is that of sulfites in alcohol. A large percentage of the population is intolerant to sulfites that can lead to irritability and headache. These compounds bind to and prevent thiamine or vitamin B1, which helps with attention, memory, and energy creation. Molybdenum 150 mcg (micrograms) daily and thiamine 100 mg daily can combat sulfite intolerance. Though thiamine is backed conclusively as a therapy around alcohol use and thiamine deficiency can cause neurologic consequences in alcoholics, the research on molybdenum is mostly bench research (animal).
Alcohol Mitigating Supplements that Start with “N,” NAC, and NAD
As stated above, I the biochemistry portion, NAD, or nicotinamide adenine dinucleotide. After a PubMed search, I could not find conclusive evidence to support supplementation as a concrete strategy to affect alcohol metabolism. N-Acetyl cysteine, on the other hand, WILL help with non-ischemic (low blood flow) states that can induce liver injury. It does smell like rotten eggs but certainly is safe for human consumption. The dose is 600 mg every 12 hours during the study sessions, and in the landmark paper of liver failure patients, this was high dose IV.
Consider Avoiding Alcohol for 14-30 Days
Of course, nothing is better than limiting alcohol or avoiding alcohol altogether. For a man, stay under, on average, three drinks in 24 hours over a week. For women, it is two drinks per day. I will tell you that it takes less to overwhelm your protective enzymatic mechanisms, and these values will likely go down.
As stated above, to properly gauge how you feel free of alcohol, you really should do this for at least 14 days (PEth). Ideally, I recommend a trial of 30 days. Not only does this reframe your relationship with alcohol, but it is the ultimate exercise in willpower. Friends and family alike will question your choices, but it is more about them and less about you. Stick to your guns, use mocktails, and seltzer water with lime to stay at the party.
Summary of The Science Behind Alcohol
Alcohol breakdown and digestion is a complex cellular process involving dehydrogenase enzymes and the reduction of NAD. Such substances can damage your cell membranes, mitochondria, and form toxic substances that can generate DNA damaging free radicles. These poisonous substances affect numerous organ systems, including your brain, heart, GI tract, and pancreaticobiliary system. You can take supplements to prevent damage to your cells and organs, but really, the data is very bioscience. The best strategy is limitation or avoidance, which should occur for at least 14 days, ideally 30 days. Plan, implement, get support, and succeed.
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