From the Guidelines
Chronic alcohol use leads to confusion and tremors due to reduced activity of alcohol dehydrogenase (ADH), the primary enzyme responsible for metabolizing alcohol, resulting in elevated levels of NADH. When alcohol consumption is chronic, ADH becomes overwhelmed, resulting in elevated levels of NADH (nicotinamide adenine dinucleotide hydrogen) 1. This elevated NADH/NAD+ ratio disrupts normal cellular metabolism, particularly affecting the liver and brain. The excess NADH inhibits gluconeogenesis, leading to hypoglycemia, and promotes lactic acid production, causing metabolic acidosis. In the brain, these metabolic disturbances, along with direct neurotoxic effects of alcohol and its metabolite acetaldehyde, contribute to confusion. The tremors characteristic of alcohol withdrawal result from increased neuronal excitability when alcohol's depressant effect is removed. This condition, known as alcohol withdrawal syndrome, can progress to delirium tremens in severe cases, requiring medical management with benzodiazepines like diazepam or lorazepam to prevent seizures and other life-threatening complications 1. Some key points to consider in the management of alcohol withdrawal syndrome include:
- The use of benzodiazepines as the 'gold standard' treatment for AWS, given their efficacy in reducing both withdrawal symptoms and the risk of seizures and/or delirium tremens 1
- The importance of evaluating the severity of AWS using tools like the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) 1
- The need for careful monitoring of vital signs and management of comorbidities in patients with AWS 1
- The potential benefits of using other medications, such as baclofen, in the treatment of AWS and prevention of relapse 1
From the Research
Chronic Alcohol Use and Enzyme Reduction
- Chronic alcohol use can lead to confusion and tremors, which are symptoms of alcohol withdrawal 2.
- The enzyme reduced in chronic alcohol use is alcohol dehydrogenase (ADH), which is responsible for ethanol oxidation 3.
- ADH catalyzes the conversion of ethanol to acetaldehyde, resulting in the reduction of NAD+ to NADH 4.
- Elevated NADH levels can lead to an imbalance in the cell's redox state, contributing to tissue damage and other metabolic disorders 4.
Enzyme Variants and Alcohol Metabolism
- Variants of the ADH and aldehyde dehydrogenase (ALDH) genes can influence drinking behavior and susceptibility to alcoholism [(5,3)].
- Some populations, such as Orientals, may lack the activity of certain ADH and ALDH isozymes, which can affect their ability to metabolize ethanol 3.
- Genetic variations in ADH and ALDH can modulate the rate of metabolism of ethanol and acetaldehyde, leading to differences in alcohol consumption and related tissue damage [(5,3)].
Alcohol Metabolism and NADH Levels
- Alcohol metabolism involves the conversion of ethanol to acetaldehyde, which is then converted to acetate 4.
- This process results in the reduction of NAD+ to NADH, leading to an increase in NADH levels 4.
- Elevated NADH levels can contribute to an imbalance in the cell's redox state, leading to tissue damage and other metabolic disorders 4.