A severe deficiency of niacin (vitamin B3) or the amino acid tryptophan can cause a severe systemic disease known as pellagra. This form of malnutrition significantly impacts cells in the skin, mouth, bowels, nervous system, and brain and can cause long-term damage to your nervous system if left untreated. 

The first report of the disease occurred in 1735 among Spanish peasants. In the United States, pellagra was very common, especially in the South, with approximately three million Americans contracting pellagra between 1907 and 1940, with many deaths. The disease remained endemic in the Southern US, Southern Europe, and the Mediterranean for many years, with its etiology being debated. In 1914, the U.S. Public Health Service’s Dr. Joseph Goldberger identified pellagra as a disease of niacin malnutrition as opposed to a contagious infectious disease. 

Today, pellagra is rare in developed countries like the United States, where B3 fortification of bread and cereal products is common, occurring in less than 1% of the population. In these settings, a niacin deficiency most commonly occurs due to malnutrition associated with alcohol use. In other regions of the world where malnutrition is more common, especially areas that depend heavily on untreated corn for food, like Africa, China, and India, pellagra occurs more frequently. 

Fortunately, a functional medicine approach can utilize advanced laboratory testing and a personalized integrative medicine management plan to replete the body of this important nutrient, while addressing reasons why malnutrition occurs.

[signup]

What is Pellagra?

If you have a severe deficiency of vitamin B3 or niacin, it can result in a systemic condition that impacts cells throughout your body. Since pellagra significantly impacts cells that require a lot of energy or turnover quickly, it has been described as causing the 3 Ds of diarrhea, dermatitis, and dementia; sometimes a fourth “D” (death) is included since this condition can have severe consequences if left untreated.

Pellagra can affect cells throughout the body, resulting in a variety of symptoms. Niacin deficiency is pronounced in areas of the body that have the highest energy requirements or cell turnover rates. These include the skin, mucosa lining the gastrointestinal tract, and nervous system/brain. Signs include weakness, mental confusion, dementia, and delusions, diarrhea, inflamed mucous membranes such as mucositis or inflammation of the oral mucosa, loss of appetite, abdominal pain, and scaly skin sores that can become infected, especially areas exposed to the sun (skin photosensitivity). The dermatitis caused by pellagra commonly results in red, flaky skin with areas of reddish or brownish discoloration, thick, crusty, scaly, or cracked skin, and patches that may itch or burn. One type of rash characteristic of pellagra is thickening and pigmentation of the skin around the neck that resembles a sunburn, known as a “casal necklace.”

If not adequately treated, pellagra can cause long-lasting damage to the nervous system and brain and even result in death.

The Role of Niacin in Body Function

Your body needs micronutrients like vitamins, minerals, and phytonutrients to carry out its optimal functioning. One such nutrient that is crucial for the function of cells throughout your body is niacin, or vitamin B3. 

This water-soluble vitamin converts food into energy. Consuming niacin-rich foods like beef liver, chicken breast, salmon, pork, rice, peanuts, pumpkin seeds, or fortified cereals or bread, allows niacin to be absorbed through the small intestine and carried to tissues throughout the body. The amino acid tryptophan can also be converted into niacin in a process that needs B2 and B6 to progress. 

Once in your tissues, niacin is converted into nicotinamide adenine dinucleotide (NAD). This coenzyme works with over 400 enzymes in your body to help them carry out important biochemical reactions. For example, coenzyme NAD is needed to transfer the potential energy from the food you eat into adenosine triphosphate (ATP) that cells need for energy to function. NAD is also essential for a variety of other cellular functions, including DNA repair, gene expression, cellular communication, and gene maintenance.

Because niacin is so vital for human health and required for these cellular processes, a deficiency of this vitamin can cause severe impacts. The skin and digestive tract are some of the tissues that require niacin for this DNA repair, so pellagra results in rough, scaly pigmented skin in areas exposed to the sun, a bright red sore tongue, and damage to the digestive tract mucosa that results in diarrhea. In addition, the brain and nervous system are especially vulnerable to a deficiency of these actions from niacin, with pellagra causing depression and apathy, headache, fatigue, and dementia that can progress to aggressive, paranoid, and suicidal behaviors and auditory and visual hallucinations.

Advancements in Lab Testing for Pellagra and Niacin Deficiency

Functional medicine laboratory testing can assess levels of niacin in the body and evaluate underlying factors contributing to this type of malnutrition. Testing can be used to help create an individualized management approach and to monitor the repletion of nutrients. 

Niacin Levels

Vitamin B3 can be measured in the blood with a single-marker test or as part of a larger panel. These traditional laboratory methods for measuring blood levels of niacin are not always accurate, so more modern diagnostic tools have been developed. 

Cutting-edge laboratory testing can more accurately assess niacin levels in the body. Modern pellagra diagnostic tests look at the levels of two breakdown products involved in niacin metabolism, which can be measured in the urine. These markers, N1-methyl-nicotinamide and N1-methyl-2-pyridone-5-carboxamide, are more sensitive and reliable ways to evaluate niacin levels in the body. When excretion rates of these two metabolites are over 17.5 micromol/day, there are generally adequate niacin supplies in the body. Still, if urinary excretion rates are less than 5.8 micromol/day, this indicates a deficiency.

Micronutrient Testing

Since pellagra is often seen along with other micronutrient deficiencies and generalized malnutrition, a general nutrition assessment can help address the whole person. Niacin, B2, B6, iron, and other nutrients can be evaluated using a Micronutrient Panel.

Amino Acid Profile

Tryptophan is an essential amino acid that is used to make niacin in a process that requires vitamins B2 and B6. The body cannot make tryptophan, so it must be acquired through the diet or via supplementation. The Amino Acid Profile by Diagnostic Solutions measures amino acid levels in plasma to identify nutrient imbalances and areas of deficiencies that can help diagnose pellagra and monitor repletion.

[signup]

Integrative Medicine's Role in Pellagra Management

An integrative medicine approach creates an individualized management plan to replenish nutrients, including niacin, and address underlying factors leading to this form of malnutrition. This holistic approach combines cutting-edge laboratory testing that can be used to develop a personalized and targeted plan of nutrition, supplementation, and lifestyle changes. 

Nutritional Recommendations

Adequate niacin can generally be obtained from a well-balanced diet focused on whole anti-inflammatory foods. The recommended daily dose of niacin is 15-20 milligrams per day and can be acquired through food like beef liver, beets, peanuts, potatoes, poultry, beef, rice, sunflower seeds, Brewer’s yeast, oily fish like salmon and tuna, and enriched bread and cereals.

When a tryptophan deficiency or malnutrition is causing pellagra, such as in the case of Hartnup disease, a high-protein diet is recommended. Foods that provide reasonable amounts of tryptophan include many of the same ones that provide niacin, such as meats like turkey, fish, and seeds. In addition, cheeses, oats, and eggs provide natural dietary sources of this amino acid. 

Since additional B vitamins, especially vitamins B2 and B6, are needed to convert tryptophan into niacin in the body, a well-rounded diet providing these nutrients can also help reverse and prevent pellagra. Foods rich in vitamin B2 include beef liver, oats, dairy products, clams, almonds, mushrooms, eggs, quinoa, salmon, spinach, apple with the skin, kidney beans, and fortified breads and cereals. Many of these foods also contain high amounts of vitamin B6.

Avoid drinking excessive alcohol to prevent malabsorption of niacin and long-term malnutrition. 

Supplementation

To treat more severe pellagra, supplementation is usually used to replete niacin levels. The niacin precursor nicotinamide is recommended by the WHO in a dose of at least 300 mg orally divided daily for 3–4 weeks. In addition, any deficiencies in B vitamins are corrected with supplementation.

If treated soon enough, improvement in symptoms of pellagra is often seen within a few days of supplementation. Some niacin supplements may cause side effects such as skin flushing, itching, rashes, bloating, indigestion, headaches, and dizziness, with many of these side effects avoided by using nicotinamide.

Lifestyle Changes

Certain groups are more at risk for pellagra. People who are undernourished because they live in poverty or have an eating disorder like anorexia, alcohol use disorder, AIDS, inflammatory bowel disease, or liver cirrhosis often do not consume enough niacin or other nutrients required to convert tryptophan to niacin such as riboflavin (vitamin B2), pyridoxine (vitamin B6), or iron. Preventing pellagra in at-risk groups like these involves rebalancing the diet and identifying when supplementation may be needed. 

In addition, resulting complications like skin and mouth sores are treated with topical emollients. It is also important to keep skin protected from the sun. In cases of secondary pellagra, it is necessary to identify and treat the underlying condition(s) causing the niacin deficiency.

Modern Challenges and Considerations in Pellagra Prevention

While most people in developed countries like the United States now consume adequate amounts of niacin, awareness, and education are needed to overcome challenges in early pellagra detection and recognize groups that remain at an increased risk of developing this form of malnutrition. Practitioners should remain aware of modern challenges, like homelessness, poverty, alcoholism, and the vulnerability that occurs amongst refugees and those caught in areas of conflict who often suffer food insecurity that predisposes them to pellagra.

When pellagra occurs due to a lack of niacin in the diet, it is termed primary pellagra. This most commonly occurs in areas of the world with high rates of malnutrition or high levels of untreated corn in their diet, as well as with malnutrition due to eating disorders like anorexia or excess alcohol use. Corn does not have much tryptophan or available niacin in it since niacin in corn is tightly bound to other components of the grain and can only be released when soaked in lime water overnight. In addition, grains such as maize and sorghum have high levels of the amino acid leucine that blocks tryptophan from being converted into niacin, resulting in niacin deficiency.

On the other hand, secondary pellagra results when your body cannot properly absorb or use the niacin you ingest. This can occur due to gastrointestinal diseases that result in malabsorption like inflammatory bowel disease or cirrhosis, HIV infection, bariatric (weight loss) surgery, malabsorption from chronic alcohol use, and certain antispasmodic and chemotherapy medications including isoniazid, pyrazinamide, 6-mercaptopurine, ethionamide, phenobarbital, azathioprine, hydantoin, and chloramphenicol. Conditions such as carcinoid tumors and the genetic condition, Hartnup disease, also result in pellagra due to insufficient tryptophan levels that cannot be converted into niacin. It can also occur along with iron deficiency anemia since iron is required for the body to convert and use niacin.

Personalized Treatment and the Future of Pellagra Management

Precision medicine offers a personalized approach that tailors evaluation and interventions to an individual’s needs. With emerging technologies, laboratory techniques, and functional medicine knowledge, an individualized approach taking into account family history, lifestyle, diet, social factors, and emotional health can be enacted. 

Personalized pellagra management strategies consider a person's genes, lifestyle habits, and environment to identify areas of risk that can be prevented and treated with an individualized approach. This approach considers the variable factors that may contribute to each person’s risk for developing pellagra and recognizes how individual differences play a role in the appropriate approach to repleting nutrients. 

Viewing health in this way allows for a more effective strategy of tailoring diet and lifestyle to meet an individual’s unique genetics, preferences, needs, and time in life. It also utilizes cutting-edge biomarker testing to help select treatments that are most likely to be effective for a specific individual and identify imbalances early on before they progress. 

[signup]

Summary

Pellagra results from a deficiency of niacin in the body that can occur due to poor intake of this B vitamin or other nutrients involved in its formation, such as tryptophan, vitamin B2, or vitamin B6. In other cases, pellagra develops due to issues absorbing or utilizing these nutrients. 

Since a deficiency of niacin especially impacts cells that turnover quickly, the most characteristic symptoms of a deficiency include diarrhea, dermatitis, and dementia. Pellagra can also cause poor appetite, abdominal pain, depression, delusions, and headaches. 

Fortunately, an integrative medicine approach that embraces modern tools for pellagra prevention and care can help combat this disease. Identifying those at greatest risk and utilizing cutting-edge laboratory testing to pinpoint areas of malnutrition allows for the implementation of a personalized and targeted prevention and treatment plan. Pellagra can usually be treated by repleting the body with adequate amounts of niacin via supplementation. Increasing awareness of this condition and those at risk is needed to ensure early recognition and supportive treatment. This is especially important since pellagra can have severe consequences and even result in death if left untreated.