Verena Briner, Switzerland
Paracelsus, a famous physician of the 16th century, wrote ‘everything is poison and nothing is poison. It is a question of the dose’. It is true in alcohol consumption. Factors such as gender, cultural reasons, comorbidities and genetics may contribute to alcohol toxicity. The danger of alcohol consumption lies primarily in alcohol addiction, leading to chronic abuse and organ damage. This results in impaired function of the brain and nerves, the heart, the liver, the pancreas, gastro-intestinal tract, immune system and metabolism. In addition, chronic heavy drinking affects family life, work and causes often economic problems.
Alcohol is absorbed fast and about 15 minutes after consumption reaches all organs of the body. Alcohol is mainly metabolized in the liver. However, in the stomach and intestine, alcohol results in the production of acetaldehyde (ACD). The ACD formed is an important factor in alcohol dependence. ACD also increases the release of mediators (histamine and bradykinin) to cause flushing. The of ACD is most severe in the brain and the heart. Abstinence from alcoholcauses increase in calcium uptake in the cells, causing arrythmia, tremor and even seizures. ACD does not pass the blood-brain barrier.
In heart muscle, alcohol causes inflammation and impairs mitochondrial function (energy machine of the cell), which predisposes to atrial fibrillation (AF). During AF, blood turbulence in the heart may lead to clots and these reach the brain via blood vessels to the brain to cause a stroke. In addition, fibrosis in the heart muscle and changes in the cytoskeleton of the cells reduce pump function. Alcoholic myopathy of the skeletal muscles occurs in about 50% of alcoholics. Atrophy of the muscle cells and low level of phosphate in the cell contribute to the loss of strength. Refeeding syndrome and rhabdomyolysis may develop when malnourished alcoholics suddenly start eating normally.
Alcohol is absorbed in the stomach (20%) and the duodenum (80%). Due to increased permeability of all the mucus membranes, food, bacterial metabolites, lipopolysaccharides (particles of bacteria) and toxins (e.g. carcinogens from smoking) all pass through the mucus membrane and enter into the interstitum to cause local inflammation of the tissue (e.g. heart burn in the oesophagus), or in the liver due to agents entering the portal vein. Alcohol induced oxidative stress also contributes to inflammation.
Alcohol is an important energy source. One gram of alcohol is 7 calories and contributes to obesity and fatty liver. Despite normal weight, alcoholics may be malnourished. Alcohol causes accumulation of fat in the liver and decrease in fatty acid oxidation. In parallel to the liver injury, blood lipid level rises and the production of proteins such as albumin and clotting factors decreases. The progression to alcoholic hepatitis and cirrhosis is most likely driven by further alcohol consumption, as well as other factors, such as the pathogens derived from the intestine after passing the leaky mucus membrane, and vitamin and micronutrients deficiency.
In animal studies, increased concentration of bacterial particles in the systemic and portal blood occurred during alcohol consumption. The intestinal bacteria (microbiome) in chronic alcohol consumption is different and impairs the mucosal immune system. Zinc, lactobacillus GG, and probiotics all have beneficial effects on the intestinal leakiness and even fatty liver disease in rodents. In the lung, alcohol inhibits the cilia motility and dirt and microbes are not cleared or only with delay. Alcohol impairs the function of immune cells, affecting both the cell-mediated and antibody-mediated immune response.
effects on the brain and nerves are caused by heavy or binge drinking of alcohol and the resulting nutritional deficiencies. The function of motor, sensory and autonomous nerves is reduced in alcoholics due to toxicity. All brain cell types are vulnerable to alcohol and its metabolites. In addition, ammonia and aromatic amino acid entering the circulation in patients with liver cirrhosis may cause hepatic encephalopathy (e.g. tremor, cognitive impairment). Heavy alcohol drinkers demonstrate degenerative processes in the brain, depression, gait disturbance, tremor, dysarthria.
Wernicke and Korsakoff syndrome are neuropsychiatric diseases in heavy, long lasting alcohol consumption. There is some overlap due to thiamine deficiency in both diseases. Wernicke encephalopathy is characterized by ophthalmoplegia, ataxia and mental confusion. In autopsies, cellular necrosis and small bleedings are observed. Sometimes Wernicke encephalopathy is misdiagnosed with acute alcohol intoxication and important treatment is delayed. Vitamin B1 (thiamine) is critical in these patients. Thiamine in high doses 3x/day should be infused to prevent progression of cerebral symptoms and brain damage. Without substitution of a high dose haemorrhages in the brain and even death may develop. Thiamine substitution may improve some of the symptoms. However, any loss of brain volume (white matter) persists. Korsakoff syndrome consists of severe memory loss.
Alcohol has toxic effect on the fetal brain. Heavy alcohol drinking pregnant women are frequently malnourished and new born babies therefore small for date. The development of the brain might be impaired even later in childhood.
Hangover occurs next morning after a rather high dose of alcohol consumption the evening before. The mechanism is not clear by which the symptoms are initiated. However, it correlates with the markers of inflammation such as TNF alpha and C-reactive protein in the blood.
Therapy options: Abstinence is key to stop damage. Withdrawal from chronic high dose of alcohol consumption causes tremor, intestinal symptoms, restlessness and even seizures. Disulfiram is used to treat alcoholism by inhibiting the metabolism of ACD, so that drinking alcohol raises ACD concentration, and causes nausea, vomiting, sweating, tachycardia. These very unpleasant symptoms discourage from alcohol consumption. Liver transplantation improves cognitive function in patients with hepatic cirrhosis but brain volume loss does not change.
|Alcohol intake and effect on the body|
|Moderate drinking||Immune response to vaccine ↑, ‘flu less frequently, beneficial effect on cardio-vascular and autoimmune diseases|
|Binge drinking||Autoregulation of the brain blood vessels ↓, may cause brain oedema, coma and even death|
|Women||4 drinks within 2 hours|
|Men||5 drinks within 2 hours|
|Heavy drinking||cirrhosis ↑, hypertension, stroke, diabetes, cancer, proinflammatory cytokine production ↑, immune function ↓ (antibody production ↓), osteoporosis, changes in gene expression
Frequently vitamin and micronutrients deficiencies
|Women||More than 60g of alcohol (6 standard drinks) on 5 or more days/month.
Or more than 7 drinks per week
|Men||More than 60g of alcohol on 5 or more days/month.
Or 14 drinks per week
|Alcohol effect on the various organs|
|Mucous membrane||barrier disruption, permeability ↑, particles enter tissue and blood vessels causing inflammation.
Pathogens enter via portal vein the liver causing inflammation there
|Oesophagus||Sphincter tone ↓ predisposing acid reflux from the stomach, inflammation of oesophagus, scarring, cancer|
|Stomach||Gastritis, ulcer causing pain and bleeding|
|Duodenum||Ulcer causing pain and bleeding|
|Intestinal microbioma||Bacteroides ↓, proteobacteria ↑, diarrhoea|
|Liver||Inflammation, steatosis, alcoholic hepatitis, fibrosis, cirrhosis and liver failure, liver cancer, hepatic encephalopathy, production of proteins ↓ (albumin and clotting factor), ↓ detoxification of portal blood from the intestine, in cirrhosis: portal hypertension and ascites|
|Pancreas||Inflammation, fibrosis and necrosis, exocrine and endocrine dysfunction and subsequent malnutrition, diabetes mellitus|
|Spleen||Liver cirrhosis increases pressure in the splanchnic blood vessels causing high pressure in the spleen and hypersplenism (platelets ↓, red blood cell lifetime ↓)|
|Rhythm||Atrial fibrillation: risk of clotting and stroke ↑|
|Heart muscle||Inflammation and interstitial fibrosis reducing ejection fraction (heart failure)|
|Blood pressure||Rises and may accelerate arteriosclerosis|
|Humoral immunity||Cytokine IL-6 & IL-12 ↓, antibody production ↓, bacterial & viral infection ↑ and more severe course of infections|
|Cellular immunity||Impaired: incidence of tuberculosis ↑|
|Central & peripheral nervous system|
|Acute toxicity of alcohol & metabolite acetaldehyde||Narcotic effect: response time ↑, cognitive impairment, sedation ↑, respiratory depression, brain oedema/bleeding , death|
|Acute hepatic encephalopathy: ammonia, aromatic amino acids, toxic lipids ↑||Confusion, delirium, slow speech, motor coordination ↓, cognitive impairment|
|Chronic alcohol: polyneuropathy||Sensor, motor, autonomous nerve function ↓|
|Alcohol tolerance||Up to 8fold after prolonged intake|
|Cilia motility ↓||Clearance of pathogens ↓, risk of infection ↑, risk of cancer ↑|
|Psychiatric disorder||Inflammation and interstitial fibrosis reducing ejection fraction (heart failure)|
|Wernicke||Trias: confusion, ophthalmoplegia (lateral gaze palsy due to brain stem lesions), ataxia (cerebellar damage). And maybe hypothermia, low blood pressure, delirium. Carbohydrate metabolism disturbed. Life threatening without thiamine treatment|
|Korsakoff||Severe memory loss, behavioural changes, irreversible brain damage|
|Thiamine/vitamin B1 in blood ↓||Absorption in the gut ↓, storage in the liver ↓|
|Melatonin in the blood ↓||Fragmentation of sleep|
|Vitamin B6, B12 in blood maybe ↓||Polyneuropathy|
|Phosphate deficiency intracellular (malnourished)||Rhabdomyolysis (muscle damage) risk of subsequent acute kidney failure|
|Hyperlipidaemia||Arteriosclerosis of the blood vessels|
|Muscle||Muscle fibre atrophy, myopathy, muscle strength ↓, sarcopenia|
|Sperm & semen||Number of sperms ↓, quality ↓|
|Haemoglobin ↓||Alcohol inhibits haemoglobin synthesis in the bone marrow, red blood cell volume increase and half-life decreases|
|Thrombocyte ↓ (platelets)||Risk of bleeding ↑|
|Oral cavity, pharynx, larynx, Oesophagus,|
|Fetal growth||Small for date baby (height and weight)|
|Cranio-facial dysmorphology||Short palpebral fissures, thin vermilion border of the upper lip|
|Behaviour change||attention deficiency, hyperactive disorder, mental retardation, reduced brain volume, delayed puperty|
|Congenital heart disease||Transposition of the large arteries|
|Epigenetic||activating and silencing gens, DNA dysregulation|