Introduction

Pellagra is a disease caused by low levels of niacin, otherwise known as vitamin B3. It may also occur l in people who have insufficient levels of the amino acid tryptophan. Tryptophan is the precursor of niacin — in other words, the liver uses tryptophan to produce niacin.¹

Alcoholism, or alcohol use disorder, involves drinking large and frequent amounts of alcohol even though you are aware of the physical and psychological harm it causes. These consequences can include physical dependency, where medical support may be needed to safely stop drinking. Treatment involves psychological intervention, alongside addressing the physical symptoms that alcohol dependence can cause.²

The link between pellagra and alcoholism

Alcoholism interferes with the metabolic pathway involving tryptophan breakdown and niacin synthesis, resulting in pellagra. Alcoholism may also cause pellagra through direct damage to microscopic structures in the gastrointestinal tract, known as intestinal villi. This leads to reduced absorption of niacin and tryptophan.³

Pellagra: causes and symptoms

Deficiency of niacin and tryptophan

Pellagra has two main causes:

1. Insufficient intake of niacin or tryptophan from the diet, known as primary pellagra
2. Failure of the body to utilise available niacin or tryptophan for normal metabolism, known as secondary pellagra

Primary pellagra is mostly prevalent in developing countries where access to food with sufficient niacin and tryptophan content is limited. Populations with a high corn-based diet are at a particularly high risk of developing pellagra because niacin can be tightly bound to the carbohydrates in corn. This results in a very low amount of niacin available for absorption.

As mentioned previously, alcoholism is a key contributor to secondary pellagra because it disrupts the metabolic pathway that synthesises niacin. Alcohol use disorder can also be destructive to the gastrointestinal tract and may further impair the absorption of niacin and other vitamins and nutrients, leading to pellagra.

Disorders of the gastrointestinal tract, such as cancer and inflammatory bowel disease, may cause secondary pellagra because these disorders reduce how much niacin can be adequately absorbed in the small intestine.

Secondary pellagra has also been shown to be caused by certain drugs. For example, isoniazid, a medication used to treat tuberculosis, reduces the activity of an enzyme known as PLP-dependent kynureninase, which is involved in niacin synthesis.^3,4

Symptoms of pellagra

The main clinical features of pellagra are referred to as the ‘3 Ds’. These include:

• Dermatitis
• Diarrhoea
• Dementia

Pellagra can eventually result in death through the following mechanism:

1. Deficiency of niacin and tryptophan
2. Insufficient energy generated through metabolic processes
3. Critical body functions cannot be adequately supported

Other pellagra symptoms

The following sections are not exhaustive but include some of the other symptoms associated with pellagra.

Gastrointestinal findings

• Glossitis, stomatitis, cheilosis
• Upper abdominal pain
• Gastritis
• Poor appetite, nausea, vomiting

Dermatological findings

• Skin redness, accompanied by a burning sensation
• Brown discolouration of sun-exposed areas of the body
• Rash on the face, neck, arms, hands, and feet

Neurological findings

• Loss of sensation, tremors
• Peripheral neuropathy
• Cerebellar ataxia, muscle weakness
• Poor concentration, fatigue

Psychological findings

• Disorientation, delirium
• Depression
• Anxiety^3,4

Alcoholism: causes and effects

Classification of alcoholism

Elvin Jellinek’s 5 Alcoholism Species is a system that classifies alcoholism based on the level of dependence. 

Physiological effects of alcohol on the body

Alcohol use disorder can negatively impact multiple organ systems and lead to an array of complications, some of which may be fatal, including:

• Cardiovascular – hypertension, atherosclerosis, arrhythmias
• Gastrointestinal – liver cirrhosis, alcoholic hepatitis, pancreatitis, gastrointestinal cancers
• Neurological and psychological – stroke, depression, anxiety, psychosis, sleep disorders, violence and aggression, suicide
• Immunological – increased susceptibility to infection^7,8

Impact of alcoholism on nutrition and vitamin absorption

Alcoholism causes malnourishment for two reasons:

1. Insufficient intake of essential nutrients and vitamins known as primary malnutrition
2. Interference with the absorption and use of these nutrients in the body is known as secondary malnutrition

The different proteins in our bodies are essential for mediating the various metabolic pathways. Alcohol interferes with the uptake of these proteins, causing multiple clinical problems. For instance, alcohol can decrease the production of albumin in the blood which may worsen blood flow through a person’s already-damaged liver. There may also be a lower amount of blood clotting factors, increasing the risk of internal bleeding in the gastrointestinal tract. Finally, alcohol reduces urea production, causing an increase in toxic ammonia levels. This puts the person at risk of developing hepatic encephalopathy.⁹ 

The link between pellagra and alcoholism

Pellagra and alcoholism have a complex relationship and both conditions share similar risk factors. We have already discussed a few of these, including poor diet, malnutrition, and gastrointestinal tract disorders.

However, there are others worth noting, such as:

• Socioeconomic factors – pellagra and alcoholism tend to impact those of lower socioeconomic status; limited access to nutritious food and lack of public education contribute to both conditions
• Mental health problems – people with alcohol use disorder often experience mental health issues such as depression and anxiety; these can worsen poor dietary choices and the malnutrition associated with pellagra¹⁰
• Liver dysfunction – the liver helps to metabolise alcohol and convert tryptophan into niacin. When this organ is damaged, the individual will become deficient in niacin and be at higher risk of developing pellagra
• Chronic inflammation – pellagra and alcoholism can lead to inflammation, which will further reduce the absorption and use of niacin in the body⁴

Diagnosis of pellagra

Pellagra is primarily diagnosed by reviewing your medical history. It is important to discuss information regarding diet, alcohol use disorder, and medications as these are key causes of pellagra. Y Your medical practitioner may also ask to perform a physical examination to check for features such as rash and skin discolouration.

There is no specific test to diagnose pellagra. However, you may be asked to supply a urine sample. If this shows that you excrete less than 0.8mg of an enzyme known as NNMT in your urine, it suggests the presence of pellagra.

The condition is also likely if you have a blood test that yields any of the following:

• Macrocytic anaemia
• Hypoproteinaemia
• Elevated liver enzymes

If pellagra is suspected, you may be given niacin supplements to see if your symptoms resolve. If this is the case, it will confirm the presence of the condition.¹¹ 

Diagnostic challenges in identifying pellagra in alcoholics 

Alcoholism can cause various medical problems of similar resemblance to pellagra, such as atopic dermatitis, gastrointestinal disorders, and cognitive dysfunction. Distinguishing between the effects of alcohol and the presence of pellagra can be challenging.

Malnutrition associated with alcoholism can manifest as deficiencies of other B vitamins besides niacin. The symptoms of these additional vitamin deficiencies can overlap with that of pellagra which can pose difficulties in making an accurate diagnosis.

Pellagra tends to develop gradually and many people with alcohol use disorder will not seek medical advice until the disease has progressed. This means that the condition is more advanced by the time it is diagnosed, making it tricky to reverse its effects.

Not all patients with pellagra will present with the ‘3 Ds’. This could lead to misdiagnosis and delayed treatment, resulting in potentially fatal consequences.¹¹

Treatment approaches for pellagra in alcoholics

Treatment of pellagra usually involves supplementation to boost levels of niacin in the body. You may be recommended a zinc supplement too. This is because zinc plays a role in the metabolism of tryptophan, and alcohol use disorder reduces zinc availability in the body. It is also advised to take particular care to use sunscreen, or to avoid sun exposure.

Finally, it is important to address the underlying cause of niacin deficiency. In the case of alcoholism, this should include addiction therapy or psychotherapy to help safely reduce alcohol intake.¹¹ 

Prevention strategies

Without treatment, pellagra can lead to complications, including cachexia, skin infections, psychological problems, coma, and eventually death.⁴ Therefore, prevention strategies and early treatment are critical so that these outcomes can be avoided.

It is important that healthcare services have nutritional support programmes in place to enable people with alcohol use disorder to access a balanced diet containing all the nutrients needed for good health.

Programmes must also offer adequate psychological support for people with alcohol use disorder so they can limit their alcohol intake, thus reducing their risk of developing pellagra. 

Summary

• Pellagra is a nutritional disorder characterised by a deficiency in niacin or tryptophan
• It is usually seen in alcoholism, because alcohol disrupts the synthesis of niacin, and damages the gastrointestinal tract to cause poor absorption of niacin and tryptophan
• Key symptoms of pellagra include dermatitis, diarrhoea, and dementia; this is referred to as the ‘3 Ds’
• Pellagra is typically confirmed by discussing the medical history
• Treatment involves nutritional supplementation as well as targeting the primary cause of the deficiency