Alcohol

Verena Briner, Switzerland

Paracelsus, a famous physician of the 16^th 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.