Macrocytosis And Alcoholism 

Overview 

Macrocytosis is the presence of abnormally enlarged red blood cells (RBCs) caused by their improper development. The term originates from the prefix “macro”, meaning large, and “cytosis”, referring to cells. In a complete blood count, the size of red blood cells is measured by the mean corpuscular volume (MCV), which is the parameter used for diagnosis. 40% of cases also involve anaemia.¹ 

Alcoholism is characterised by a loss of control over alcohol consumption or an excessive desire to drink. Alcohol misuse negatively impacts health over time and can also lead to social problems, such as strained relationships with friends, family, or colleagues. As nutritional insufficiencies are common in alcohol use disorders, they can contribute to macrocytosis due to the absence or lack of essential vitamins required for RBC development.^1,2  

This article will provide insights into the symptoms, treatments, and complications associated with these conditions.  

Pathophysiology of macrocytosis 

Macrocytosis can have several different causes, including: 

• Deficiencies in vitamin B12 or folate 
• Liver disease 
• Hypothyroidism (underactive thyroid) 
• Certain drugs, such as chemotherapeutic medicines 

These factors can lead to the production of megaloblasts abnormally large red blood cells that arise from improperly divided precursors.³  

Defining the relationship between alcoholism and macrocytosis 

Ethanol, the ingredient in alcoholic beverages that causes intoxication, inhibits protein synthesis, which is essential for red blood cell formation (erythropoiesis).³ Erythropoiesis is a complex process in which a progenitor cell must undergo multiple changes before it can enter the bloodstream to deliver oxygen to respiring tissues.  

During this process, immature red blood cells (normoblasts) become smaller as they mature into red blood cells.⁴ The process of erythropoiesis can be affected by alcohol both directly and indirectly. 

Folic acid is essential for proper erythropoiesis, as it supports the production of proteins necessary for cell replication. However, alcohol directly alters the absorption of folic acid from food. It is common for alcoholics to have poor dietary habits, which may not contain sufficient folic acid in the first place. A lack of folic acid leads to faulty or dysfunctional proteins that impair the normal division of red blood cell progenitors. Consequently, nonfunctional, large red blood cells accumulate in the bone marrow and circulation.⁵ 

When we consume alcohol, it is broken down by the liver. During this process, both the liver and blood are subjected to oxidative stress from metabolites- the products generated by alcohol breakdown.⁶  While alcohol is filtered out, some liver cells (hepatocytes) are damaged or killed in the process. Reactive oxygen species generated from ethanol metabolism can harm the liver and decrease its regenerative capacity.⁷ Repeated heavy drinking can lead to alcoholic liver disease.  

Though macrocytosis itself presents no immediate issues, untreated alcoholism can result in a poor prognosis.  

Clinical presentation and diagnosis 

The first step used to identify macrocytosis is collecting a blood sample. It will be sent to the lab for analysis of different parameters, including MCV. The blood sample can reveal anaemia and vitamin deficiencies also. After macrocytosis is identified, your doctor will perform a physical examination, obtain a health history and assess your symptoms. Since macrocytosis without anaemia can overlap with signs of alcohol misuse, your doctor will look for signs such as:

• Fatigue  
• Shortness of breath 
• Pallor (unusually pale skin) 
• Jaundice (yellowing of the skin and eyes) 
• Liver issues, such as hepatitis or cirrhosis (scarring of the liver) 
• Arrhythmias (irregular heartbeat) 

To determine if macrocytosis is the result of alcoholism, other causes of elevated MCV must be ruled out.⁸ Your physician may order the following tests to get a clearer picture of your health: 

• Peripheral smear 
• Reticulocyte count (measuring the number of immature red blood cells in the bone marrow) 
• Serum B12 level 

If the peripheral smear comes back normal, your doctor may suspect that macrocytosis is related to alcoholism. As a result, they may also ask you about your drinking habits.⁸ 

Management and treatment 

Measures can be taken to reduce alcoholism and provide your body with the correct nutrients.  

According to the UK Government, as of 2020, it is estimated that over 600,000 people in the UK are dependent drinkers.⁹ If you struggle with drinking, there are plenty of resources available to help you. The first step typically involves detoxification, but it can also include counselling and support groups. Alcohol addiction services in your area can be found on the NHS website. Alternatively, you can seek help online or by telephone:  

• Drinkline, the UK’s national alcohol helpline, is completely confidential. They can be reached at 0300 123 1110 from 9 am to 8 pm on weekdays, and 11 am to 4 pm on weekends 
• Alcoholics Anonymous is a free service that provides a 12-step programme dedicated to achieving sobriety through regular support groups 
• We Are With You is a UK-based treatment agency that helps individuals and families manage the effects of drug and alcohol misuse 
• SMART Recovery helps individuals recognise and change their behaviour, offering personalised motivation tools 

Controlling alcohol intake is the best way to reduce the risk of developing chronic liver disease and heart damage.¹⁰ 

Nutritional support can help increase levels of vitamin B12 and folate, facilitating normal erythropoiesis and reducing symptoms associated with alcoholism.¹¹   

Monitoring and long-term follow-up allow us to track macrocytosis and alcohol use: 

• Treatment can be monitored through  regular MCV measurements to ensure red blood cells are the correct size 
• For dependent drinkers, regular support can help improve control over drinking habits 

Abstinence will aid in the recovery process, and with proper treatment, macrocytosis is reversible. Cessation of alcohol use can cause macrocytosis to resolve within a few months.¹² 

Prognosis and complications 

Since alcoholism is an underlying cause of macrocytosis, chronic and systemic complications can arise if left untreated:¹³

• Increased risk of anaemia, along with related issues such as dizziness and shortness of breath 
• Liver cirrhosis (fibrosis of the liver) 
• Cardiomyopathy (weakening of the heart muscle) 
• Stroke 
• Elevated blood pressure 
• Pancreatitis (inflammation of the pancreas) 
• Cancer of the oral cavity, oesophagus, liver, breast, and colorectal region 
• Changes in behaviour and mood, such as aggression 
• Weakened immune system  

By reducing alcohol use, these risks can be avoided. While macrocytosis may present few symptoms on its own, it is still important to regulate your alcohol consumption as part of a healthy lifestyle. Though challenging, the benefits of reducing alcohol intake far outweigh the negatives. In fact, alcoholic macrocytosis without anaemia or liver disease is relatively benign. Acting early is essential to maintaining good health, and the presence of macrocytosis can be an early sign of excessive alcohol misuse.¹

Summary 

Macrocytosis refers to the enlargement of red blood cells and is measured by MCV. Excessive alcohol consumption can interfere with the formation of blood cells, leading to the appearance of large, abnormal cells. When these cells are released into the bloodstream, they can cause fatigue or changes in skin appearance. Diagnosing alcoholic macrocytosis involves using tests to rule out other causes of enlarged blood cells. Treatment then focuses on reducing alcohol consumption and improving nutrient intake, specifically vitamin B12 and folic acid. Managing alcoholism as early as possible reduces the risk of severe health problems, such as liver cirrhosis and anaemia.  

It can be challenging to take steps toward changing alcohol habits, but online resources and real-life support can make a positive difference both physically and mentally. Be open to conversations with loved ones, and remember that they are on your side. 

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Reijance Salvador

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