Food Fighting and Curing Disease Series: Pellagra

Advancing the Integration of Food as Medicine in Modern Healthcare Using Proof from the Past

What is Pellagra?

Pellagra is a disease that occurs when the body is deficient in niacin (vitamin B3).¹ The word Pellagra translates to “sour or rough skin” in Italian, as darkening, itchy skin known as dermatitis is one of the first and most telling symptoms of the disease.² Other symptoms include dementia, depression, and eventual death, together known as “The 4 D’s”.¹ Niacin, (vitamin B3), an essential nutrient, finds its natural sources in meats, poultry, fruits, and vegetables.¹ Niacin can be supplemented through vitamins or in severe cases, injections.² The encouraging facet lies in the fact that Pellagra, when identified in its initial stages, exhibits a degree of reversibility.² Within developed nations, the prevalence of Pellagra has markedly diminished, largely attributed to shifts in dietary patterns and the widespread practice of fortifying flour with niacin.²

“Pellagra is a nutritional disorder caused by niacin (vitamin B3) deficiency, which leads to systemic disease with clinical manifestations from the skin, gastrointestinal tract and the nervous system.”²

History 

Early Findings

Pellagra was first described in Spain in the 1700s, where its victims were marked by the emergence of dense, black rashes adorning their necks.³ Initially misinterpreted, the condition was erroneously believed to be an infectious malady.³ Progressing into the early 20th century, Pellagra cast a profound shadow of mortality on a global scale, particularly afflicting regions in Europe and Africa.³

The year 1735 marked a significant turning point in the understanding of Pellagra when it was initially identified in Spain, where peasants began suffering from distressing rashes.⁴ In the early stages, physicians mistakenly linked Pellagra with leprosy.⁴ It wasn’t until the 1900s that the dietary connection to Pellagra was established.⁴

Pellagra in the United States

The United States South found itself grappling with alarming instances of Pellagra during the early 1900s.³ This issue stemmed from the prevailing monoculture farming practices in the region, which focused primarily on cultivating cotton.³ This agricultural monoculture led to a limited diversity in the diets of the local population.³  It primarily affected impoverished populations who relied heavily on corn-based diets, especially in states like South Carolina.⁴ Dr. Joseph Goldberger, a U.S. Public Health Service physician, played a crucial role in understanding the disease’s dietary origins.⁴ He theorized that Pellagra might be linked to poor diet and malnutrition.⁴

By the year 1912, the state of South Carolina alone had identified a staggering 30,000 cases of Pellagra, with a distressing fatality rate of 40%. This alarming situation spurred the need for a more comprehensive investigation into its underlying causes.⁴ 

The Thompson-McFadden Pellagra Committee

In response, the formation of the Thompson-McFadden Pellagra Committee in 1914 aimed to identify effective treatments for this ailment.⁵ Named after its proponents, Robert M. Thompson and Henry McFadden—respectively a mining tycoon and a cotton merchant—the committee raised funds to conduct a comprehensive investigation.⁵ This involved door-to-door surveys of South Carolina residents in cotton mill villages, where self-reported food consumption and Pellagra incidence were documented.⁴ However, the committee erroneously concluded that Pellagra was infectious due to its clustering pattern.⁴

Dr. Joseph Goldberger’s Progressive Insights

Dr. Joseph Goldberger, an epidemiologist with the United States Public Health Service, took a different approach.⁴ Drawing from his experience in curing typhoid and other infectious diseases, he challenged the idea that Pellagra exhibited characteristics of an infectious ailment.⁴ Goldberger’s astute observations in asylums and orphanages across different socio-economic strata revealed distinct diets among residents.⁴ A pivotal experiment showcased that Pellagra was in fact linked to dietary insufficiency.⁴ Transitioning individuals with deficient diets—marked by low protein and inadequate intake—to a wholesome and balanced diet led to the reversal of Pellagra symptoms.⁴ Strikingly, reverting these individuals to a nutrient-deprived diet resulted in a 40% resurgence of Pellagra symptoms.⁴ In contrast, those benefiting from well-balanced diets remained free from Pellagra.⁴

Goldberger’s subsequent experiment at the South Carolina State Penitentiary involved deliberately exposing inmates to suspected Pellagra-causing diets.⁴ Intriguingly, guards with better diets, even in close proximity to Pellagra-stricken prisoners, remained unaffected.⁴

These unethical experiments, which would not be allowed under modern ethical guidelines, led to important discoveries about the link between diet and the disease.⁵ While the commission’s methods may be viewed critically today, its findings significantly contributed to our understanding of nutritional deficiencies and the importance of a balanced diet in maintaining public health.⁵

Conrad A. Elvehjem: Finding The Connection Between Niacin (Vitamin B) Deficiency and Pellagra

While the specific identification of niacin (vitamin B3) as the essential nutrient to prevent Pellagra did not occur until 1937, the realization that dietary deficiency underpinned Pellagra had a monumental impact on saving numerous lives.⁴ The credit for connecting niacin (vitamin B3) deficiency to Pellagra goes to Conrad A. Elvehjem, who, through experiments on dogs with black tongues, discovered that administering niacin orally resulted in a reversal of their condition.³ This breakthrough insight translated seamlessly to humans afflicted by the same ailment.³

Significance of Niacin (Vitamin B3)

Niacin (Vitamin B3) is essential for metabolism.¹ Specifically, it facilitates the crucial oxidation-reduction reactions within cells, which are necessary in order for the body to use energy.¹ Apart from its primary function, niacin also plays a multifaceted role in blood sugar regulation, DNA synthesis, and the maintenance of healthy skin.¹ Upon entering the body, niacin undergoes a conversion by cells, ultimately yielding NAD and NADP, which serve as coenzymes.¹ 

NAD stands for Nicotinamide Adenine Dinucleotide, and NADP stands for Nicotinamide Adenine Dinucleotide Phosphate. These coenzymes play pivotal roles in various biochemical processes, serving as electron carriers and facilitators of energy transfer within cells.

The NAD coenzyme is intricately involved in reactions that transform proteins, fats, and carbohydrates into the energy currency of the body, namely ATP.¹ This energy is indispensable for various physiological processes.¹ On the other hand, NADP contributes to the synthesis of fatty acids, another critical aspect of cellular function.¹ 

Recommended Dietary Allowance of Niacin (Vitamin B3)

As per information from the USDA, instances of niacin deficiencies in the United States are currently uncommon, owing to the extensive practice of enriching grains with niacin as well as diversity in diet.¹ This concerted effort has significantly curbed the prevalence of such deficiencies.¹

According to the USDA’s Recommended Daily Allowance (RDA), adult men are advised to aim for an intake of 16 mg of niacin, while adult women should target 14 mg.¹ However, for women who are lactating, the recommended intake increases to 17 mg daily, and for those breastfeeding, the advised amount is 18 mg daily.¹

Niacin, an essential nutrient, can be sourced naturally from an array of foods, incorporated deliberately into others, and is also available in supplement form when dietary sources prove insufficient.¹ This multifaceted availability ensures that individuals have enough ways to guarantee adequate niacin.¹ 

Causes & Risk Factors 

Pellagra occurs as a result of not consuming enough niacin (vitamin B3).¹ Niacin is most concentrated in meats and poultry, but is also found in fruits, vegetables, and fortified grains.¹ In developing countries where food is not fortified with niacin and diets are not be as varied, Pellagra is common.¹ 

Niacin deficiency occurs when not enough niacin and/or tryptophan are consumed.¹ Tryptophan is an amino acid which is necessary in the breakdown, or metabolism, of niacin.¹ If someone is severely malnourished then they may be lacking in the nutrients that help convert tryptophan to niacin, also resulting in niacin deficiency.¹ The nutrients needed to convert tryptophan to niacin include vitamin B2, vitamin B6, and iron, so a deficiency in any of these three vitamins could also cause niacin deficiency.¹

People who do not have enough nutrients, including people with anorexia nervosa, AIDS, chronic alcohol usage, cirrhosis, or inflammatory bowel disease, are at risk of having low niacin.¹ People with Hartnup Disease have issues transporting amino acids throughout their bodies, which impacts the transport of tryptophan in the body, resulting in poor niacin metabolism, causing Pellagra.¹ Carcinoid Syndrome is another disease linked with Pellagra – it results in the metabolism of tryptophan to serotonin instead of niacin, so the body has less niacin available and thus Pellagra can occur.¹

Symptoms

“The pellagra syndrome has historically been characterized by the 4 D’s: Dermatitis, Diarrhea, and Dementia leading to Death.”²

Symptoms include:¹ 

 

• • Pigmented rash or brown discoloration on skin that gives a rough, sunburn-like appearance

• • Black or bright red tongue

• • Vomiting

• • Constipation 

• • Diarrhea

• • Apathy

• • Headache

• • Fatigue

• • Loss of memory

• • Anorexia

• • Death

Food as Medicine – Natural Sources of Niacin (Not Enriched) 

Food	Serving Size	Amount (mg) of Niacin (Vitamin B3)	Percent Daily Value
Beef liver	3 oz	14.9 mg	100%
Chicken	3 oz	10.3 mg	64%
Tuna	3 oz	8.6 mg	61%
Salmon	3 oz	8.6 mg	61%
Pork	3 oz	7.38 mg	52%
Turkey	3 oz	6.3 mg	45%
Brown rice	1 cup	5.2 mg	37%
Beef tenderloin	3 oz	5.3 mg	36%
Peanuts	1 oz	4.2 mg	30%
White potato	1 medium	2.3 mg	16%
Sunflower seeds	1 oz	2.0 mg	14%
Lentils	1/2 cup	1.0 mg	7%
Bananas	1 medium	0.8 mg	6%

This chart, which lists the top naturally occurring niacin-rich foods, is made with data from the USDA.⁶

Contemporary Understanding 

According to the USDA’s guidelines, nutritional needs for niacin should be met completely through diet.¹ It is recommended that individuals consume a variety of foods, including high protein foods, and limit alcohol intake to ensure adequate niacin (vitamin B) intake.¹

Modern Medical Intervention: Shifting Perspectives on Pellagra Causes and Treatment

For people suffering from Pellagra, the World Health Organization recommends taking 300 mg of nicotinamide orally every day for three to four weeks.¹ The oral nicotinamide is a water-soluble form of niacin and is absorbed easily by the body.¹ This treatment is often supplemented with yeast products or a Vitamin B multivitamin in order to ensure there are other B-vitamins present in the body to help with metabolism.¹ After treatment patients are advised to maintain a healthy, varied diet.¹ The effects of taking oral nicotinamide occur quickly and individuals can experience a complete or near complete recovery from symptoms if treatment is administered early enough.¹ 

In the era preceding the 21st century, nutritional deficiency stood as the primary catalyst behind the occurrence of Pellagra.³ However, with the advent of fortification practices and an increased diversity in dietary choices, the landscape has transformed. In developed nations, the primary cause of Pellagra is no longer rooted in nutrient scarcity.³ Instead, contemporary causative factors have shifted towards conditions and elements that hinder the proper absorption of niacin or tryptophan.¹

For individuals suffering from Pellagra, the World Health Organization recommends taking 300 mg of oral nicotinamide, a water-soluble form of niacin (vitamin B), daily, spanning three to four weeks.¹ This form of niacin (vitamin B) is readily assimilated by the body, ensuring swift absorption.¹ Typically this treatment is supplemented by yeast products or a vitamin B multivitamin to guarantee the presence of other B-vitamins essential for metabolic processes.¹ Following the treatment periods, patients are advised to maintain a balanced and diverse diet.¹ Remarkably, the effects of oral nicotinamide administration manifest quickly, often leading to a complete or near-complete alleviation of symptoms, particularly if the treatment is initiated promptly.¹

Pellagra Today: Evolution of Pellagra Trends 

Within developed nations, the occurrence of Pellagra has become exceedingly rare, primarily due to the widespread fortification of grains.³ Even on the rare occasions when instances of Pellagra emerge, they are largely attributed to secondary factors impeding the body’s niacin absorption.³ These contemporary hindrances encompass conditions such as anorexia nervosa, severe alcoholism, malabsorption syndrome, or adverse drug effects.³

However, the prevalence of Pellagra remains notable in certain regions such as African nations, India, and certain parts of China.³ Recent reports have also surfaced of refugees grappling with Pellagra. Consequently, individuals who have endured periods of malnutrition are advised to undergo assessments for low niacin levels and subsequently supplement as required.³ For instance, in Thailand, the traditional diet provides only 13% of the recommended dietary intake of niacin, leading to widespread niacin deficiency.³ Similarly, a recent study in India unveiled that 13% of adolescent girls exhibited niacin deficiency.³ Remarkably, despite corn being a staple crop in Africa, Pellagra still persists – an investigation discovered that one-third of women in Angola showcased symptoms of Pellagra.³ 

Remarkable studies have been made in treating Pellagra through the administration of oral doses of nicotinamide, a water-soluble variant of niacin (vitamin B3).³ In just a span of three weeks, significant recovery effects have been witnessed in Pellagra patients.³ While Pellagra bears the potential for fatality, it is crucial to recognize that it is a treatable condition – one that can be reversed through timely detection and appropriate intervention.²

Anecdote – Early American Maize Preparation

The Native Americans in Mexico and North America did not suffer from Pellagra, yet their European colonizer counterparts who consumed the same maize, got Pellagra.⁷ 

What secret did the Native Americans have?

There was no secret – just a special preparation for the maize called nixtamalization.⁷ This process involved soaking the dried corn in an alkaline solution before cooking it.⁷ Normally this solution was lime water.⁷ Using the lime water breaks down the corn in such a way that the tryptophan (which can be converted by the body into niacin) in it becomes bioavailable to consumers.⁷ If nixtamalization is not performed on maize, then all of the niacin that is in the corn will not be able to be consumed by the body.⁷ Native Americans would leave out bowls of lime water with corn, yet Spanish explorers ignored the process and instead suffered the effects of Pellagra for the next 200 years.⁷ 

Anecdote – Wonder(ful) Bread

Surprisingly, there was a time when nutritionists held a fondness for Wonder Bread – a staple that adorned grocery store shelves for two decades prior to the pivotal “flour hearings” convened by the Food and Drug Administration in 1940.⁷ Against the backdrop of World War II, these hearings aimed to combat the rampant malnutrition crisis sweeping through the United States.⁷ Amid the myriad of solutions proposed, one particularly transformative idea emerged: the fortification of flour with vitamin B, including niacin, vitamin B3.⁷ This enriched flour, in turn, found its way into the creation of none other than Wonder Bread.⁷

By the year 1943, a remarkable shift had transpired – enriched flour had become the foundation of 75% of the bread stocked in American grocery stores.⁷ In an astonishingly short span of time, the specter of Pellagra, which had loomed over the United States, receded into near oblivion. Notably, Wonder Bread’s popularity surged both during and after World War II, earning it the emblematic status of a “victory food.”⁷ 

Databases

 

• • Niacin Deficiency (National Institutes of Health, 2023)

• • Office of Dietary Supplements – Niacin (National Institutes of Health, 2023)

• • Niacin (United States Department of Agriculture, 2018)

Research Studies

 

• • Pellagra: A Review Exploring Causes and Mechanisms, Including Isoniazid-Induced Pellagra (Wiley Online Library, 2021) 

• • Pathophysiology and Clinical Management of Pellagra: A Review (Department of Dermatology, 2021) 

• • Pellagra in South Africa from 1897 to 2019: a scoping review (Cambridge University Press, 2021)

• • Pellagra secondary to selective eating in a child with autism (Wiley Online Library, 2020)

• • The 4 D’s of Pellagra and Progress (Sage Journals, 2020)

• • Corn, Niacin, and the History of Pellagra (Nutrition Today, 2020)

• • Pellagra, an Almost-Forgotten Differential Diagnosis of Chronic Diarrhea: More Prevalent Than We Think (Wiley Online Library, 2019)

• • Pellagra: A Forgotten Entity (Clinical Dermatology Review, 2019)

• • Pellagra and anorexia nervosa: a case report (Springer Link, 2019)

• • The Rise and Fall of Pellagra in the American South (Cambridge University Press, 2019)

• • Recognizing the return of nutritional deficiencies: a modern pellagra puzzle (BMJ Journals, 2018)

• • Pellagra Affecting a Patient with Crohn’s Disease (Scientific Electronic Online Journal, 2017)

• • Alcoholic Pellagra as a Cause of Altered Mental Status in the Emergency Department (The Journal of Emergency Medicine, 2017)

• • Pellagra Secondary to Medication and Alcoholism (Nutrition in Clinical Practice, 2016)

• • Pellagra and Alcoholism: A Biological Perspective (Alcohol and Alcoholism, 2014)

• • Pellagra: A Non-Eradicated Old Disease (Clinics and Practice, 2014)

• • Pellagra. A challenging differential diagnosis (Journal of Tissue Viability, 2014)

• • An unexpected case of pellagra (The Medical Journal of Australia, 2014)

News and Media

 

• • Vitamin B3: How did one vitamin get so many names? (Cashmere Valley Record, 2023)

• • 100 years ago, country paid homage to ‘hero’ scientist (McDonald County Press, 2023)

• • Lessons from time: What millet advocates can learn from an 18th-century epidemic disease (The Economic Times, 2023)

• • Vitamin B3: Benefits, Sources, and Side Effects (Healthnews, 2023)

• • What is tryptophan? (Verywellhealth, 2023)

• • Niacin History (News Medical Life Sciences, 2023)

• • Niacin Deficiency (News Medical Life Sciences, 2022)

• • Pellagra (The New England Journal of Medicine, 2022)

• • Understanding Niacin Deficiency (Verywellhealth, 2022)

• • Hunger in the Heart of Empire: Pellagra in the United States (Elephant, 2021)

• • Why do we need vitamin B-3, or niacin? (Medical News Today, 2020)

• • Persistent Diarrhea, Delirium, and Beefy Tongue: Is It Pellagra? (Medical Professionals Reference, 2019)

• • The rise of Arfid: the truth about the eating disorder that made a teenager go blind (The Guardian, 2019)

• • Vitamin-Packed with Promises (New York Times, 2018)

• • Cultural Ignorance: Lost Indigenous Recipe Could Have Prevented Pellagra Epidemic (Public Media Group of Southern California, 2017)

• • Cleveland: Pellagra and the history of the South (Chattanooga Times Free Press, 2016)

• • How Wonder Bread Saved Civilization (Chicago, 2014)

Key Words

Searched on Google, Google News,  Google Scholar, and PubMed, with search terms:

Pellagra (Google Scholar, Filter 2014-2023)

Pellagra (Google News) 

Pellagra (PubMed, Filter 2014-2023) 

Niacin + Deficiency (Google Scholar, Filter 2014-2023)

Niacin-containing foods (Google Scholar, Filter 2014-2023)

Pellagra + News (Google Scholar, Filter 2014-2023)

Pellagra + History (Google Scholar, Filter 2014-2023)

Pellagra + Treatment (Google Scholar, Filter 2014-2023)

Pellagra + Symptoms (Google Scholar, Filter 2014-2023)

Pellagra + Trial (Google Scholar, Filter 2014-2023)

Conrad A. Elvehjem (Google Scholar, Filter 2014-2023)

Historical Treatment of Pellagra (Google Scholar, Filter 2014-2023)

Pellagra + Niacin (Google Scholar, Filter 2014-2023)

Pellagra + Today (Google Scholar, Filter 2014-2023)

Pellagra + Developing countries (Google Scholar, Filter 2014-2023)

Pellagra + Developed countries (Google Scholar, Filter 2014-2023)

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