Recognising the return of nutritional deficiencies: a modern pellagra puzzle
A 34-year-old previously well woman presented with a 4-week history of diffuse erythema and crusting of skin affecting all four limbs. Examination revealed erythematous skin plaques associated with ulceration and fissuring affecting sun-exposed areas of all four limbs primarily on the dorsal surfaces, and a body mass index of 17 kg/m2. She was admitted under the infectious diseases unit, and an autoimmune and infective screen was performed which returned unremarkable. Dietetic consultation led to the diagnosis of severe protein-energy malnutrition, consequent to a severely restricted, primarily vegan, diet. Analysis of the patient’s reported diet with nutritional software revealed grossly suboptimal caloric intake with risk of inadequacy for most micronutrients, vitamins and minerals, including niacin[B-3]. Oral thiamine[B-1], multivitamin, iron supplementation and vitamin B complex were started, and a single intramuscular vitamin B12 dose was administered. Marked improvement was seen after 6 weeks, with near-complete resolution of skin changes. These findings supported a diagnosis of pellagra.
In the northern Italian town of Ferrara hangs a little-known painting by Giuseppe Mentessi (1857-1931). Surrounded by a field of maize, a woman carries her exhausted child in her arms, her eyes downcast with suffering. Behind this painting lies a story of medicine, food, economics, and culture – the story of pellagra, perhaps one of the greatest tragedies of malnutrition known to the Western world.
Exhibited at the Venice Biennale in 1895, Mentessi’s image of a cornfield depicts what once was a common sight throughout the region. Maize or corn was first domesticated as a cereal crop in the Americas, making its way to Europe via traders in the sixteenth century.1 This new foodstuff proved to be a lifeline for Italian agricultural workers who labored under the pressures of wheat shortages and insecure employment.2 With its low cost and high yield, cornmeal or polenta was quickly established as the staple food of the poor. Landowners were eager to profit from maize production, and eventually forests, vineyards and pastures across the Veneto and Lombardy were replaced by fields of this single crop. It was fitting that Mentessi named his picture “Our Daily Bread” – for by the 1800s, northern Italian peasants were living on a diet made up almost exclusively of corn.2
At the same time, increasing numbers of them were falling victims to a new disease. Characterised by a flaking rash on the sun-exposed skin of the arms and neck, they named it pellagra (from pelle agra, loosely translated as “rough skin”).3 Symptoms included confusion, mania, lethargy, and eventual death. While the link between pellagra and maize dependence was quickly recognized by scientists at the time, the mechanism remained a mystery. Today, we know that pellagra is a disease of severe niacin (vitamin B3 or nicotinic acid) deficiency. Niacin is the precursor of two essential coenzymes of cellular activity – nicotinamide adenine dinucleotide (NAD) and NAD-phosphate (NADP) – both involved in DNA repair, cell signalling, and metabolism.4 Tissues with high energy requirements and high cell turnover are particularly vulnerable to their deficiency. Without sufficient dietary niacin – or tryptophan, the amino acid used in its biosynthesis – a systemic disease occurs affecting the skin, gastrointestinal tract, and nervous system. The resulting clinical features have been famously described as the 4 D’s: dermatitis, diarrhea, dementia, and death.4
The unvarying cornmeal diet that poor Italians relied on in the lean winter months, without the addition of vegetables, dairy products, or meat, was severely deficient in both niacin and tryptophan.
Individual cases of the deficiency disease are occasionally found in chronic alcoholics, elderly widowers who have an improper food intake, and inpatients suffering from malabsorption. ~[WHO]Pellagra, its Prevention and Control in Major Emergencies.
An epidemic of pellagra resulted, with thousands of deaths attributed to the illness – particularly in women, who had increased nutritional needs because of pregnancy and breastfeeding, and whose inferior social position meant that they tended to have less food then the men in their family.2 So common did the neuropsychiatric effects of the illness become, that mental asylums such as Venice’s San Servolo and San Clemente were full of victims of what was then termed “pellagrous insanity.”3 For almost two centuries, pellagra was endemic in the agricultural lands of the Po valley across northern Italy.1
It was this widespread suffering which Giuseppe Mentessi sought to depict in his painting. Born into poverty in Ferrara, Mentessi went on to have a successful career as an art teacher and professor at the Accademia di Brera in Milan.5 Nevertheless, his work maintained a deep affinity with his humble origins and he often used his art to highlight the social issues of the day. In “Our Daily Bread,” he shows the misery of the Italian rural poor, with the woman’s sickly countenance a mark of the effects of pellagra. What he depicted in paint, the writer Goethe described in words in his ‘Italian Journey:’ “Of the (Italian) inhabitants, I have little to say and that unfavourable … (the) sallow complexion of the women spoke of misery and their children looked just as pitiful … I believe that their unhealthy condition is due to their constant diet of yellow polenta …”6
It was not the diet of cornmeal alone which gave rise to pellagra in southern Europe, but also the method of preparation. While maize had been a staple food of central America for thousands of years, the indigenous peoples were accustomed to soaking the dried corn kernels in alkaline lye or quicklime before cooking. This process, known as “nixtamalization,” increased the bioavailability of bound niacin in the corn by converting it into the water-soluble free compound, allowing it to be absorbed by the gut.7 As a result of their traditional cultural methods of preparation, the native people of the Americas did not suffer from pellagra.
When corn was brought across the Atlantic to Europe, the tradition was lost. Furthermore, pellagra was then introduced to the Americas, where European colonizers grew and ate corn without realizing the benefit of nixtamalization or the importance of a varied diet. Particularly in the Southern states, in the economic downturn following the American Civil War, the daily fare for poor people consisted almost entirely of corn-based products such as cornbread and grits. Rural sharecroppers and populations lacking access to fresh produce – in prisons, coal-mining camps, and cotton-mill towns – were particularly vulnerable to niacin deficiency. The devastation occurred on a grand scale; across the United States from 1906 to 1940 approximately 3 million cases and 100,000 deaths were attributed to pellagra.8
It was a US public health physician, Joseph Goldberger, who determined that pellagra was a nutritional deficiency and not (as was commonly supposed) an infectious epidemic. In 1915, he carried out a series of experiments in Mississippi prisoners which demonstrated that symptoms of pellagra appeared after six months of eating only corn-based foods; when fresh, varied produce was introduced, the illness resolved. He concluded that “no pellagra develops in those who consume a mixed, well-balanced diet,” yet struggled to convince the political establishment that poor social conditions might be responsible for the disease.9 It took several more decades of research – including the isolation of niacin itself from liver tissue by Conrad Elvehjem in 1937 – before federal recommendations to fortify flour supplies with vitamins led to the eradication of the condition in the United States by 1945.7
In Italy, economic growth helped end the pellagra epidemic during the 1950s, but not before the illness had provoked widespread debate about the impact of social injustice and deprivation on human health, with commentators such as Flarer (1849) referring to pellagra as “malattia del padrone” – “illness due to the landlord.”1 Today, we understand more than ever the impact of socio-economic factors on our health, with recognition that the West’s adoption of a highly-processed, energy-dense diet has contributed to our modern epidemics of obesity and diabetes. Such “malnutrition in the midst of plenty” has echoes of Mentessi’s work. It is said that he had the idea for his painting when he was taking an afternoon walk through a field of corn and was struck by the contrast between the bountiful crop and the sickly peasant woman with her child: “misery, perhaps hunger, in the middle of that insolent and healthy wealth!”10 In both Europe and the United States, it is still the poorest sections of society who suffer the most from their dependence on an abundance of cheap calories. While it may have been largely forgotten, the story of pellagra ought to be a lasting lesson in how social structures, globalization, and economic change once conspired to cause thousands of deaths from an entirely preventable disease.