10+ Reasons Why Alcohol Intolerance Happens And How To Build Alcohol Tolerance (Mechanisms And Genetics)
Are you someone who could handle their alcohol until getting sick, then any sort of alcohol in any amount may make you feel sick?
This is a common problem with those after their immune system has gone haywire.
In this post, I will breakdown and discuss mechanisms behind the loss of tolerance towards alcohol and how to rebuild tolerance.
Basics About Alcohol Intolerance
A few factors play a role in alcohol intolerance, but the critical factor here is the inability to metabolize the alcohol and its metabolites properly.
This problem is usually worse after having a major challenge to the system (infection, sensitization, etc).
For example, those with Chronic Fatigue Syndrome (CFS) usually have to reduce or completely eliminate alcohol from their diet. R
Why Does Alcohol Intolerance Happen?
1. Metabolism of ACD/ADH/ALDH and NAD+ Loss (Most Common)
Alcohol dehydrogenase (ADH) is the main enzyme that converts alcohol into a more toxic byproduct called Acetaldehyde (ACD) and then less toxic metabolites:
Alcohol via (ADH)→ ACD (via ALDH) → Acetate (+CoA) → Acetyl-CoA → CO2 + H2O
^ This process uses up NAD+ and those with chronic illness (mitochondrial dysfunction) may have difficulty producing sufficient NAD+… this means that ACD is allowed to build up. R
Also via the Cori Cycle, this loss can block the process of gluconeogenesis in the liver, in which its mechanism is to take lactic acid and convert it back to glucose for reuse by the glycolysis pathway in the cells. R
This means for those who do not product enough NAD+ may get lactic acidosis and hypoglycemia when drinking alcohol.
Some parts of alcohol are also converted via Cytochrome P450 enzyme MEOS/CYP2E1.
ALDH deficiency may cause alcohol flush reaction via the accumulation of ACD. R
The alcohol flush reaction is a common problem in those with Asian descent.
In rs671 encoding ALDH2 (I’m GG):
Mutations in ALDH (Asians) and ADH1 (other parts of population) can also cause alcohol-induced respiratory reactions. R
2. Disulfiram Reaction
As stated earlier, ALDH loss causes a buildup of ACD, and Disulfiram (drug) is used in animal models to induce the “unpleasant effects” of alcohol - this reaction is called a Disulfiram Reaction. R
3. Immune Sensitization
It has been shown that individuals with severe hypersensitivity reactions to ethanol have elevated levels of circulating anti-acetaldehyde– protein IgE antibodies. R
In these studies, the acetaldehyde moiety has been shown to be acting as a hapten. R
4. FXR And Broken Detox Mechanisms (Common After Bioaccumulation)
As alcohol is transported and distributed throughout the body - blood, brain, liver (90% metabolism here), kidneys, bone, etc - having any problems (such as injury to the liver) may cause alcohol intolerance. R
Liver injury may be a common mechanism in those with chemical sensitivities that have intolerance to alcohol. R
For example, alcohol exposure impairs folate absorption (inhibits expression of the reduced folate carrier and decreasing the hepatic uptake and renal conservation of circulating folate). R
At the same time, folate deficiency accelerates alcohol-induced changes in hepatic methionine metabolism while promoting enhanced oxidative liver injury. R
Alcohol can also produce symptoms in those that are deficient in Glutathione (GSH, eg via catalase), as cysteine/methionine is used in multiple systems such as the methylation cycle and BHMT pathway. R
The Farnesoid X Receptor (FXR) also acts on the liver (via pyruvate dehydrogenase kinase 4 (PDK4)) and alcohol can inhibit FXR, thus promoting of bile into the intestines and if you are toxic (dysbiosis, fatty liver, bioaccumulation, etc) you may feel worse since you’re essnetially re-poisoning yourself. R R
5. Prostaglandins And Oxidative Stress
One example, Isoprostanes (prostaglandin-like compounds from the free radical-catalyzed peroxidation of essential fatty acids) are increased in patients with Alcohol-induced Liver Disease (ALD). R
Another example, ROS can promote alcohol-induced sensitization of liver cells via TNF-alpha. R
Those with sugar intolerances may not be able to handle the sugars in alcohol. (speculation in clients)
Proteins in alcohol [prolamins - wheat (gliadin), barley (hordein), rye (secalin), corn (zein), sorghum (kafirin) and oats (avenin)] may also trigger autoimmune symptoms (via zonulin) as alcohol can increase intestinal permeability (leaky gut), thus allowing prolamines and other these proteins into the blood. R R
This above mechanism is highly dependent on the microbiome, for example, alcohol can suppress Lactobacillus strains, while E. coli and Weissella confusa strains can also produce alcohol in the gut. R
7. Aldosterone, Cortisol, Blood Pressure And Electrolytes
Sphingosine-1-Phosphate (S1P) can stimulate cortisol and aldosterone secretion (from Phosphatidic Acid (PA) via Phospholipase D (PLD). R
Alcohol reduces PA and forms Phosphatidylalcohol (via PLD). R
If S1P signaling is impaired (low S1P levels or auto-receptor-antibodies to S1P) alcohol maybe be messing with cortisol and aldosterone, and thus cause a fluid/electrolyte/blood pressure imbalance. R
Any acute xenobiotic chemical exposure that changes brain function may manifest in poor symptoms.
In the brain alcohol acts primarily via: R
↑GlyR (also reuptake inhibition)
9. Additives, Preservatives, And Naturally Occurring Compounds
Certain additives such as sulfites can cause poor reactions in those sensitive (including dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhea). R
Sulfites may also contribute to thiamine deficiency due to the breakdown of thiamine present as sulfite’s ability to limit the production of thiamine by certain gut bacteria. R
Benzoates have been linked to chronic urticaria, asthma, atopic dermatitis, rhinitis and anaphylaxis. R
Monosodium glutamate (MSG) has been linked to asthma, headache, urticaria and angioedema, rhinitis, psychiatric disorders and convulsions. R
Salicylates are common in wines and salicylate sensitivity/intolerance can cause a variety of adverse symptoms. R
10. Other Reasons
Poorly distilled alcohols can have byproducts (acetone, ethyl acetate, methanol, propanols, esters, etc) which may cause poor reactions.
I’ve heard some people talk about mold in alcohol (poor distillation) although I haven’t seen strong evidence to support this.
For those with Post Exertional Malaise (PEM), exercise causes increase in aldehydes, specifically Malondialdehyde (MDA), similar to acetaldehyde.
Prospective Tests For Alcohol Intolerance
Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) R
My Experience With Alcohol Intolerance
After having dysbiosis for many years, my ability to metabolize alcohol had become worse and I would always get flushing (low ALDH) and headaches (additive problems and FXR/bile dumping) almost immediately after drinking.
Now, after working on my detox mechanisms (in section above), my tolerance to handle more alcohol has significantly increased - this makes participating in social gatherings easier, although I am not a huge fan of the “drunk” feeling.
I drink mostly fruit-based alcohols, such as tequila or cider (low sulfites or sulfite-free) from time to time.
How To Increase Alcohol Tolerenace
Apart from alcohol avoidance (obviously), here is a list of supplements and foods that may help with the excretion of alcohol/metabolites (may have no effect on hangover).
Elaeagnus conferta - increases the activity of ADH R
Musa acuminata - significanty increases the activity of ADH R
Nicotinamine Riboside - ALDH reaction in the liver requires NAD, which can be in short supply in ME/CFS.
Prunus cerasus/Techtochrysin - accelerates ACH metabolism by inducing ALDHs R
Stay Away From:
Acyclovir/Valcyclovir (Valtrex) R
Coca Cola R
Citron Tea - reduces ethanol but increases ACD R
Daidzin and Daidzein R
Disulfiram (Antabuse) R
Jasmine Tea R
Java apple (Syzygium samarangense) R
Kudzu (Pueraria lobata) R
Lemon Juice - reduces ethanol but increases ACD R
Orange Juice - reduces ethanol but increases ACD R
Nifurtimox, or 5-nitrofuran R
Pesticides - captan, folpet, thiram, ziram, and benomyl—resulted in at least a 15% reduction in ALDH activity compared to baseline values R
Plum Juice - reduces ethanol but increases ACD R
Red Bull - reduces ethanol but increases ACD R
Solvents - paints, cosmetics, sunscreens, and dyes; such as ethyl tertiary-butyl ether (ETBE) - chronic exposure may lead to acetaldehyde accumulation R
Water Chestnut Juice R