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Pellagra in the United States: A Historical Perspective
Abstract
Pellagra was in existence for nearly two centuries in Europe before being recognized in the United States, where it was first reported in 1902. Over the next two decades, pellagra occurred in epidemic proportions in the American South. Poverty and consumption of corn were the most frequently observed risk factors. Since the exact cause and cure of pellagra was not known, a culture of "pellagraphobia" formed among the public. Patients were shunned and ostracized. The medical community implicated spoiled corn as the cause of pellagra, which had economic repercussions for agriculturists. Joseph Goldberger, MD, of the United States Public Health Service eventually solved the secret of the malady: faulty diet. Goldberger was able to prevent and induce pellagra by dietary modification, a landmark event in the annals of medicine, nutrition, and epidemiology. His work and the social history of that period are reviewed.
... The dietary deficiency disease had been erroneously presumed by physicians, public health officials and politicians to be caused by an infectious pathogen or spoiled corn and even failed to notice and/or acknowledge the social epidemiological underpinnings of race, gender, and economic status as risk factors in the etiology and/or pathogenesis of the nutrient deficiency disease (Marks, 2003;Mooney et al., 2014;Rajakumar, 2000). The victims were predominantly African American and over two-thirds were women who lived and worked under very poor conditions in the cotton, tobacco and corn growing countryside of the southern states of the USA (Marks, 2003;Park, Sempos, Barton, Vanderveen, & Yetley, 2000). ...
... Mesoamerican corn with them from Latin America back home, could have avoided the massively debilitative consequences of pellagra on millions of Europeans, had they been aware of the import and usefulness of nixtamalization commonly used by the Latin Americans to process maize into nixtamal dough, popularly used for the production of delicacies like tortillas (Rajakumar, 2000). ...
... The impact of the lack of, or inadequacy of an individual nutrient, or a combination of a few essential nutrients especially limiting essential amino acids (LEAAs), vitamins and minerals in cereals, if not supplemented by some viable means with the preformed essential nutrient such as through dietary fortification, it could prove to be nutritionally problematic (Kaufman, 1990). Pellagra, scurvy, beriberi, rickets, and Kwashiorkor are examples of dietary deficiency diseases owing to the lack of, or inadequate intake of one, or a few combinations of some critical nutrients (Elmore & Feinstein, 1994;Martin & Humphreys, 2006;Rajakumar, 2000). ...
... By the 1930s, pellagra (a disease of niacin deficiency) had claimed the lives of more than 100,000 Americans and had severely affected more than 3 million. 5 Yet by mid-century, the diseases of nutritional deficiency had been largely eradicated and the nutritional and health status of Americans was steadily improving. ...
... 81 In the early part of the 20th century, despite the correlational evidence pointing to genetic factors and infectious agents, it was established that diets chronically deficient in niacin caused pellagra. 5,82 The history of pellagra may be illuminating because the political use of the correlational evidence appears to have impeded scientific progress and harmed public health. 82,83 Despite nutrition science's history of overcoming the inherent flaws of correlational research (e.g., bias, confounding, ecological fallacy) through the use of rigorous scientific research, in the 2015 DGAC report, the distinction between correlation and causation is obscured. ...
... This result is incorrect by an order of magnitude. 135 In 2009, an 18-month randomized, 5. The stark reality that traditional weight-management programs are ineffective can be considered at least a partial indictment of the historical effectiveness of government dietary guidelines. ...
... The first case of pellagra in the United States was documented in 1902 where the disease quickly developed into an epidemic impacting farming communities in the southern states for over four decades. In this time, estimates suggest there were 3 million cases and 100,000 deaths (86,193). ...
... In 1914, Joseph Goldberger noted that pellagra occurred in inmates of mental institutions whose diet consistent of vegetables and cereals while the staff members, whose diet was more varied and included more meat and dairy products, were 16 FESSEL AND OLDHAM unaffected. In a series of human experiments, Goldberger showed that dietary manipulations could both cure and induce pellagra (193). Based on prior investigations, Conrad Elvehjem et al. demonstrated that commercial preparations of nicotinic acid and nicotinamide were highly effective at curing dogs of ''black tongue,'' a canine manifestation of pellagra (55). ...
... Based on prior investigations, Conrad Elvehjem et al. demonstrated that commercial preparations of nicotinic acid and nicotinamide were highly effective at curing dogs of ''black tongue,'' a canine manifestation of pellagra (55). As a result of these and other studies, public awareness campaigns, agricultural diversification, and food fortification with nicotinic acid, pellagra was eradicated in the South by 1945 (193). Currently, sporadic cases of pellagra occur in developed countries among people dependent on drugs or alcohol, food faddists, or patients with malabsorption states, while cases continue to occur in developing areas where corn products are the major food source (86). ...
Significance:
Pyridine dinucleotides, NAD and NADP, were discovered over 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases. Recent Advances: A biochemistry renaissance in biomedical research, with its increasing focus on the metabolic pathobiology of human disease, has reignited interest in pyridine dinucleotides which has led to new insights into the cell biology of NAD(P) metabolism, including its cellular pharmacokinetics, biosynthesis, subcellular localization, and regulation. This review highlights these advances to illustrate the importance of NAD(P) metabolism in the molecular pathogenesis of disease.
Critical issues:
Perturbations of NAD(H) and NADP(H) are a prominent feature of human disease; however, fundamental questions regarding the regulation of the absolute levels of these cofactors and the key determinants of their redox ratios remain. Moreover, an integrated topological model of NAD(P) biology that combines their metabolic and other roles remains elusive.
Future directions:
As the complex regulatory network of NAD(P) metabolism becomes illuminated, sophisticated new approaches to manipulating these pathways in specific organs, cells, or organelles will be developed to target the underlying pathogenic mechanisms of disease, opening doors for the next generation of redox-based, metabolism-targeted therapies.
... By the 1930s, pellagra (a disease of niacin deficiency) had claimed the lives of more than 100,000 Americans and had severely affected more than 3 million. 5 Yet by mid-century, the diseases of nutritional deficiency had been largely eradicated and the nutritional and health status of Americans was steadily improving. ...
... 81 In the early part of the 20th century, despite the correlational evidence pointing to genetic factors and infectious agents, it was established that diets chronically deficient in niacin caused pellagra. 5,82 The history of pellagra may be illuminating because the political use of the correlational evidence appears to have impeded scientific progress and harmed public health. 82,83 Despite nutrition science's history of overcoming the inherent flaws of correlational research (e.g., bias, confounding, ecological fallacy) through the use of rigorous scientific research, in the 2015 DGAC report, the distinction between correlation and causation is obscured. ...
... This result is incorrect by an order of magnitude. 135 In 2009, an 18-month randomized, 5. The stark reality that traditional weight-management programs are ineffective can be considered at least a partial indictment of the historical effectiveness of government dietary guidelines. ...
... Pellagra is a systemic disease resulting from a marked chronic deficiency of Vitamin B3 (niacin) and/or nicotinamide [1][2][3]. Niacin and nicotinamide are precursors of coenzyme I (the oxidized form of nicotinamide adenine dinucleotide (NAD)) and coenzyme II (the reduced form of nicotinamide adenine dinucleotide phosphate (NADP), which either donate or accept hydrogen ions in vital oxidation-reduction reactions [1][2][3]. A pellagra diagnosis should focus on the presence of the "3 D's" (diarrhea, dermatitis and dementia), localization and seasonal appearance. ...
... Pellagra is a systemic disease resulting from a marked chronic deficiency of Vitamin B3 (niacin) and/or nicotinamide [1][2][3]. Niacin and nicotinamide are precursors of coenzyme I (the oxidized form of nicotinamide adenine dinucleotide (NAD)) and coenzyme II (the reduced form of nicotinamide adenine dinucleotide phosphate (NADP), which either donate or accept hydrogen ions in vital oxidation-reduction reactions [1][2][3]. A pellagra diagnosis should focus on the presence of the "3 D's" (diarrhea, dermatitis and dementia), localization and seasonal appearance. ...
... Previous work has sought to document the connection between cotton production and pellagra by using simple time series and cross-sectional comparisons. These correlations show that when and where cotton production was high so too was the pellagra rate (Park et al. 2000;Goldberger, Wheeler, and Sydenstricker 1920;Rajakumar 2000). However, ascribing causality to the positive correlation between cotton production and pellagra is problematic. ...
... The importation of food into the South would tend to increase pellagra if the food being imported had lower levels of niacin than locally grown food. Indeed, historical observers often attribute the increase in pellagra to changes in the milling of Midwestern corn (e.g., Park et al. 2000;Goldberger, Wheeler, and Sydenstricker 1920;Rajakumar 2000). Previous milling technology had removed less of the germ, retaining some niacin. ...
Focusing on the first half of the twentieth century, we explore the rise and fall of pellagra (a disease caused by inadequate niacin consumption) in the American South. We first consider the hypothesis that the South’s monoculture in cotton undermined nutrition by displacing local food production. Consistent with this hypothesis, a difference in differences estimation shows that after the arrival of the boll weevil, food production in affected counties rose while cotton production and pellagra rates fell. The results also suggest that after 1937 improved medical understanding and state fortification laws helped eliminate pellagra.
... Hallucinations often triggered an admission to a psychiatric hospital, and insanity was quickly followed by death. Knowledge of pellagra spread and caused those who were sick to be shunned and ostracized (Rajakumar, 2000). Some affected individuals took their lives to avoid the feared insanity. ...
... Between 1907 and the early 1940s, pellagra affected N 3 million individuals in the South, with N100,000 deaths (Rajakumar, 2000). By the 1950s, pellagra had nearly vanished, and although rarely seen today, pellagra continues to occur in the context of malabsorption (i.e., Crohn's disease; Hui et al., 2017), alcoholism (Luthe and Sato, 2017), malnutrition, (i.e., eating disorders) and exposure to certain medications (i.e., azathioprine, isoniazid; Zhao et al., 2018). ...
... Pellagra presents with some of or all the 3 D's: dermatitis, diarrhoea and dementia (or more appropriately delirium, see Oldham and Ivkovic, 2012) and excellent reviews have been published on historical and clinical aspects (e.g. Rajakumar, 2000;World Health Organisation, 2000;Wan et al., 2011). I should like to add here a biochemical perspective, with particular emphasis on metabolism of the essential amino acid tryptophan (Trp), as it is the precursor of the pellagrapreventing factor nicotinic acid (niacin: also known as vitamin B 3 ). ...
... Pellagra in India has been associated with intake of maize and another staple, jowar (a variety of sorghum). In the Southern USA, pellagra became a serious medical problem following the American civil war, due to subsistence on a largely maizebased staple (Rajakumar, 2000). It was in the USA around the middle of the 20th century that most studies on the aetiology, prevention and cure of pellagra were undertaken. ...
Historical and clinical aspects of pellagra and its relationship to alcoholism are reviewed from a biochemical perspective. Pellagra is caused by deficiency of niacin (nicotinic acid) and/or its tryptophan (Trp) precursor and is compounded by B vitamin deficiencies. Existence on maize or sorghum diets and loss of or failure to isolate niacin from them led to pellagra incidence in India, South Africa, Southern Europe in the 18th century and the USA following the civil war. Pellagra is also induced by drugs inhibiting the conversion of Trp to niacin and by conditions of gastrointestinal dysfunction. Skin photosensitivity in pellagra may be due to decreased synthesis of the Trp metabolite picolinic acid → zinc deficiency → decreased skin levels of the histidine metabolite urocanic acid and possibly also increased levels of the haem precursor 5-aminolaevulinic acid (5-ALA) and photo-reactive porphyrins. Depression in pellagra may be due to a serotonin deficiency caused by decreased Trp availability to the brain. Anxiety and other neurological disturbances may be caused by 5-ALA and the Trp metabolite kynurenic acid. Pellagra symptoms are resolved by niacin, but aggravated mainly by vitamin B6. Alcohol dependence can induce or aggravate pellagra by inducing malnutrition, gastrointestinal disturbances and B vitamin deficiencies, inhibiting the conversion of Trp to niacin and promoting the accumulation of 5-ALA and porphyrins. Alcoholic pellagra encephalopathy should be managed with niacin, other B vitamins and adequate protein nutrition. Future studies should explore the potential role of 5-ALA and also KA in the skin and neurological disturbances in pellagra.
... The 4 "D's" of Dementia, Dermatitis, Diarrhoea and Death are taught to medical students but the interesting history of pellagra and its wider phenotype is largely forgotten [1][2][3][4]. A characteristic blank facies and a festinating gait, fasciculation of the tongue or myoclonic encephalopathy are classic features of well-known neurological diseases that were actually first described in the pellagra epidemics. ...
Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt about the diseases and social and economic consequences of poverty – and for the root cause of poverty (and of affluence) – that involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption from genotoxic, infectious and metabolic stresses. NAD deficiency is closely linked to poor physical and intellectual development, premature ageing and diseases of ageing. Acute infections, many with NAD-consuming toxins, that may differentially affect the NAD-depleted, now include COVID-19. Some Covid manifestations, such as myoclonic encephalopathy and “Long Covid,” resemble pellagra clinically and biochemically as both have disturbed nicotinic and tryptophan metabolism. Symbionts that supply nicotinic acid, such as TB and some gut micro-organisms, can become dysbiotic if the diet is very deficient in milk and meat, as it is for 1–2 billion or more. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome: this gives a mechanism for an unrecognised hypervitaminosis-B3 with adverse effects of nicotinamide overload for consumers on a high meat diet with “fortified” foods and “high energy” drinks. Methods of measuring NAD metabolism routinely for screening the populations at risk of deficiency and in metabolically ill or infectious disease patients should be developed urgently. Successful intervention should improve human capital and prevent many aspects of poverty, reduce discrimination and even the drive to emigrate.
... As the NAD + pool is turned over several times per day in various tissues and cell types [8], an adequate supply of both NAD + precursors, including nicotinamide, and NAD + biosynthetic enzymes are essential for cell vitality. Sustained sub-optimal intracellular NAD + levels have been shown to have long-term physiological consequences, while depletion of NAD through nutritional deficiency leads to pellagra, a debilitating and deadly disease still endemic in some regions of the world [9,10]. Newer biomedical rationales have driven attention to NAD + biosynthesis, as NAD homeostasis depends on age [11]. ...
Nicotinamide adenine dinucleotide (NAD+), the essential cofactor derived from vitamin B3, is both a coenzyme in redox enzymatic processes and substrate in non-redox events; processes that are intimately implicated in all essential bioenergetics. A decrease in intracellular NAD+ levels is known to cause multiple metabolic complications and age-related disorders. One NAD+ precursor is dihydronicotinamide riboside (NRH), which increases NAD+ levels more potently in both cultured cells and mice than current supplementation strategies with nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) or vitamin B3 (nicotinamide and niacin). However, the consequences of extreme boosts in NAD+ levels are not fully understood. Here, we demonstrate the cell-specific effects of acute NRH exposure in mammalian cells. Hepatocellular carcinoma (HepG3) cells show dose-dependent cytotoxicity when supplemented with 100–1000 μM NRH. Cytotoxicity was not observed in human embryonic kidney (HEK293T) cells over the same dose range of NRH. PUMA and BAX mediate the cell-specific cytotoxicity of NRH in HepG3. When supplementing HepG3 with 100 μM NRH, a significant increase in ROS was observed concurrent with changes in the NAD(P)H and GSH/GSSG pools. NRH altered mitochondrial membrane potential, increased mitochondrial superoxide formation, and induced mitochondrial DNA damage in those cells. NRH also caused metabolic dysregulation, altering mitochondrial respiration. Altogether, we demonstrated the detrimental consequences of an extreme boost of the total NAD (NAD+ + NADH) pool through NRH supplementation in HepG3. The cell-specific effects are likely mediated through the different metabolic fate of NRH in these cells, which warrants further study in other systemic models.
... Pellagra is a debilitating disorder caused by the deficiency of niacin and/or its precursor tryptophan. Symptoms of pellagra were first documented in 18 th century by the Spanish doctor Gasper Casal, who described a disorder attributed to a diet deficient in meat [92]. Pellagra was epidemic in malnourished regions of Europe and the southern states of the United States of America. ...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that has garnered considerable interest in the last century due to its critical role in cellular processes associated with energy production, cellular protection against stress and longevity. Research in NAD+ has been reinvigorated by recent findings that components of NAD+ metabolism and NAD-dependent enzymes can influence major signalling processes associated with the neurobiology of addiction. These studies implicate raising intracellular NAD+ levels as a potential target for managing and treating addictive behaviour and reducing cravings and withdrawal symptoms in patients with food addiction and/or substance abuse. Since clinical studies showing the use of NAD+ for the treatment of addiction are limited, this review provides literature evidence that NAD+ can influence the neurobiology of addiction and may have benefits as an anti-addiction intervention.
... Then, there are three important things that should be considered in designing the reflective teaching activities, namely: a) aim, b) evidence and reflection, and c) extension. Bannister (1996) defined Costumer Education as the process of gaining the knowledge and skills to manage personal resources and to participate in social, political and economic decisions that affect individual well being and the public good. Consumer Education pays close attention to the awareness building and information transmission for changing individual's behaviors (McGregor, 2005). ...
Formal education plays a big role in the construction and development of students’ competence and skill. A survey on the fashion engineering education in Indonesia found that most students had not appropriately applied the competence and skill they learned. Many of them did not say anything despite experiencing loss, were reluctant to ask for exchange or compensation, littered the product’s waste, and had no interest in using do-it-yourself (DIY) skills to make their own products. Therefore, this study is aimed at depicting the importance of learning the Consumer Education materials, the application of living values in the Consumer Education materials, and the effectiveness of consumer living values on students’ character-building. In this survey-based study, the ex post facto approach was used in order to evaluate the results of Consumer Education learning through reflective assessment sheet. The research population was 123 students of Fashion Engineering Education Study Program in higher education institutions in Yogyakarta Province who had passed the Consumer Education course in the odd semester in Indonesia in 2017. The sample was established through the stratified proportional random sampling technique, while the descriptive statistical analysis was applied to the findings of reflective assessment. The results show the students agree that learning Consumer Education course is imperative for day-to-day life and the Consumer Education materials are found to be effective in consumers’ character-building. This study has not internalized of the values through advice, example, discussion, role playing, and participation in the activities of consumption events around daily life. Further studies are needed for developing a relevant curriculum, training in designing content, strategies, instruments, and evaluation of learning.
... Pellagra, a disease provoked by chronic deficiency of niacin, became an epidemic in both the USA and Europe as a consequence of a diet based mostly on corn [1]. Strangely, corn contains significant levels of niacin. ...
... As the whole, consumer education is very important for consumers' selfp r o t e c t i o n a n d e m p o w e r m e n t a n d educational programmes should focus on consumer literacy for guarding the rights and responsibilities of consumers under the law (Bannister, 1996;Wan, Kamariah, Norela, & Halimah, 2001). Nevertheless, the difficulty is that there are no standard indicators to determine legal literacy, and therefore, this article intends to explain the domains and indicators of consumer legal literacy based on Malaysian law. ...
Legal literacy is one of the important aspects of consumer empowerment. The objective of this paper is to determine the domains and indicators of legal literacy in Malaysia. The methodologies used are a combination of qualitative and quantitative research. The qualitative method utilised a Focus Group Discussion (FGD) technique, while the data for quantitative method were gathered through a survey. The findings of the FGD reveal that there are eight domains of consumer legal literacy that are based on consumer rights. The rights are the right to basic needs, the right to safe goods and services, the right to information, the right to make a choice, the right to be heard, the right to get compensation, the right to consumer education and the right to life in a healthy and safe environment. However, the results of the factor analysis revealed five domains, which are the right to safe and quality goods and services, the right to compensation, the right to consumer education, the right to be informed of financial matters and the right to be heard and to obtain information. Altogether, there are 46 indicators for measuring consumer legal literacy. The domains and indicators can be used to develop a Malaysian Legal Literacy Index and provide the instruments for measuring legal literacy in Malaysia.
... Goldberger made significant efforts to isolate the so-called pellagra-preventing factor for which he was nominated for the Nobel Prize in Physiology and Medicine. He died in 1929 and it was the American biochemist Conrad Elvehjem who discovered soon after that niacin was capable of preventing pellagra [2]. This discovery was of crucial importance in building up a pellagra-prevention campaign, along with a food-fortification programs. ...
... In 1870, frequent pellagra outbreaks among poor populations in southern and central Europe had followed the introduction of maize. At the end of the 19th and the beginning of the 20th centuries, pellagra reached epidemic proportions among the population of the southern United States and became the most severe deficiency disease in the history of the United States, with more than 120,000 deaths by the 1920s (Etheridge, 1972;Rajakumar, 2000). Joseph Goldberger, working for the United States Public Health Service in the 1920s, discovered that milk and meat could provide a pellagra-preventing (PdP) factor, which was absent in corn. ...
Nicotinic acid and nicotinamide, collectively referred to as niacin, are nutritional precursors of the bioactive molecules nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are important cofactors for most cellular redox reactions, and as such are essential to maintain cellular metabolism and respiration. NAD also serves as a cosubstrate for a large number of ADP-ribosylation enzymes with varied functions. Among the NAD-consuming enzymes identified to date are important genetic and epigenetic regulators, e.g., poly(ADP-ribose)polymerases and sirtuins. There is rapidly growing knowledge of the close connection between dietary niacin intake, NAD(P) availability, and the activity of NAD(P)-dependent epigenetic regulator enzymes. It points to an exciting role of dietary niacin intake as a central regulator of physiological processes, e.g., maintenance of genetic stability, and of epigenetic control mechanisms modulating metabolism and aging. Insight into the role of niacin and various NAD-related diseases ranging from cancer, aging, and metabolic diseases to cardiovascular problems has shifted our view of niacin as a vitamin to current views that explore its potential as a therapeutic.
... Deficiency of niacin and/or tryptophan contributes to pellagra. Diets rich in corn contain less niacin and tryptophan, contributing to the development of pellagra [113]. Patients with pellagra show AE-like erythema, diarrhea, and dementia [114]. ...
The skin is the third most zinc (Zn)-abundant tissue in the body. The skin consists of the epidermis, dermis, and subcutaneous tissue, and each fraction is composed of various types of cells. Firstly, we review the physiological functions of Zn and Zn transporters in these cells. Several human disorders accompanied with skin manifestations are caused by mutations or dysregulation in Zn transporters; acrodermatitis enteropathica (Zrt-, Irt-like protein (ZIP)4 in the intestinal epithelium and possibly epidermal basal keratinocytes), the spondylocheiro dysplastic form of Ehlers-Danlos syndrome (ZIP13 in the dermal fibroblasts), transient neonatal Zn deficiency (Zn transporter (ZnT)2 in the secretory vesicles of mammary glands), and epidermodysplasia verruciformis (ZnT1 in the epidermal keratinocytes). Additionally, acquired Zn deficiency is deeply involved in the development of some diseases related to nutritional deficiencies (acquired acrodermatitis enteropathica, necrolytic migratory erythema, pellagra, and biotin deficiency), alopecia, and delayed wound healing. Therefore, it is important to associate the existence of mutations or dysregulation in Zn transporters and Zn deficiency with skin manifestations.
... In the late 1920s, Joseph Goldberger fed Brewer's yeast to dogs with pellagra; a devastating disease characterized by dermatitis, diarrhea, dementia and death, and their health improved. At that time, pellagra was endemic in parts of the United States, and so the Red Cross supplemented Brewer's yeast to its food rations in pellagra-endemic areas, and within weeks the disease burden dissipated 2,3 . The health significance of NAD+ was established in 1937 when Conrad Elvehjem and his colleagues made the major discovery that the factor that prevented and cured pellagra was the NAD+ precursor, nicotinic acid 4,5 . ...
Nicotinamide Adenine Dinucleotide (NAD+) is an established cofactor for enzymes serving cellular metabolic reactions. More recent research identified NAD+ as a signaling molecule and substrate for sirtuins and poly-ADP polymerases; enzymes that regulate protein deacetylation and DNA repair, and translate changes in energy status into metabolic adaptations. Deranged NAD+ homeostasis and concurrent alterations in mitochondrial function are intrinsic in metabolic disorders such as type 2 diabetes, non-alcoholic fatty liver and age-related diseases. Contemporary NAD+ precursors show promise as nutraceuticals to restore target tissue NAD+, and have demonstrated the ability to improve mitochondrial function and sirtuin-dependent signaling. This review will precis the accumulating evidence for targeting NAD+ metabolism in metabolic disease, map the different NAD+ boosting strategies and discuss the challenges and open questions in the field. The health potential of targeting NAD+ homeostasis will inform clinical study design to identify nutraceutical approaches for combating metabolic disease and the unwanted effects of aging.
... Golberger proved that pellagra was dietary in origin and due to a lack of meat and milk, not genetic or infectious, and that eventually influenced thinking that southerners were not genetically degenerate and deserved help. 166,167 Finally, the biochemical basis and treatment with replacement nicotinic acid was discovered in the 1940s. 168 ...
Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.
... What caused pellagra, and what could be done to treat it or prevent it? The history tells us something about scientific errorsand if, when, and how they are corrected (Rajakumar, 2000;Marks, 2003;Mooney et al., 2014). ...
... Nixtamalization increases available niacin in maize and also increases tryptophan, which allows more niacin to be formed. Pellagra was widespread in many areas of Europe in the eighteenth and nineteenth centuries, in the southeastern US in the early twentieth century, and still occurs today in poor populations of Africa, Asia, and Latin America (FAO 1992;Rajakumar 2000;Roe 1973). However, there is no evidence that it occurred among indigenous populations in the western hemisphere before colonization (Fussell 1999;Roe 1973). ...
span>Scholars have studied The Three Sisters, a traditional cropping system of the Haudenosaunee (Iroquois), from multiple perspectives. However, there is no research examining food yields, defined as the quantities of energy and protein produced per unit land area, from the cropping system within Iroquoia. This article compares food yields and other nutrient contributions from the Three Sisters, comprised of interplanted maize, bean and pumpkin, with monocultures of these same crops. The Three Sisters yields more energy (12.25 x 106 kcal/ha) and more protein (349 kg/ha) than any of the crop monocultures or mixtures of monocultures planted to the same area. The Three Sisters supplies 13.42 people/ha/yr. with energy and 15.86 people/ha/yr. with protein. Nutrient contents of the crops are further enhanced by nixtamalization, a traditional processing technique where maize is cooked in a high alkaline solution. This process increases calcium, protein quality, and niacin in maize.</span
... Over two centuries ago, a Spanish doctor Gasper Casal described a disease in poor farmers, whose diet was poor in meat and mainly dependent on Indian corn or maize [1]. This disease was characterized by dermatitis, diarrhea, dementia and death and was later termed pellagra [2]. ...
We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proof of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health.
... The name is not without meaning. The first case of pellagra was reported in the U.S. in 1902; four decades of a pellagra epidemic followed during which, in states south of the Potomac and Ohio rivers, some 3 million cases and 100,000 deaths were reported [1]. Pellagra patients presented with a variety of debilitating symptoms including, significantly, a spectrum of cutaneous lesions. ...
... On the other hand, it should be noted that excess sweat vitamin excretion may cause or worsen watersoluble-vitamin deficiency if there is poor vitamin intake. A good example may be pellagra, a niacin-deficiency disease that affects those who live in poverty without sufficient animal-source foods (rich in nicotinamide), with the symptoms occurring during the summer [38] , a season with the highest sweat excretion rates. However, over the past decades, both natural and artificial sources (i.e., vitamin fortification and supplementation) of vitamins have significantly increased [2] , while sweat excretion has significantly decreased due to physical inactivity and the widespread use of air conditioning. ...
Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.
... In the United States alone, pellagra (a disease of niacin deficiency) claimed more than 100,000 lives and severely affected more than 3 million people. 4 Yet in 2013, the Centers for Disease Control and Prevention's Second National Report on Biochemical Indicators of Diet and Nutrition reported that nearly "80% of Americans (aged 6 y) were not at risk of deficiencies in any of the 7 vitamins" 4,p938 examined via biomarkers (ie, vitamins A, B 6 , B 12 , C, D, E, and folate; emphasis added). 2 In addition, approximately 90% of women of childbearing age (12-49 years) were not at risk for iron deficiency, and folate levels have increased by approximately 50% since the previous national report. 2,5 As such, most of the US population is not at risk for nutritional deficiencies, and For editorial comment, see page XX neither do they have nutritional deficiencies and associated diseases. ...
The Scientific Report of the 2015 Dietary Guidelines Advisory Committee was primarily informed by memory-based dietary assessment methods (M-BMs) (eg, interviews and surveys). The reliance on M-BMs to inform dietary policy continues despite decades of unequivocal evidence that M-BM data bear little relation to actual energy and nutrient consumption. Data from M-BMs are defended as valid and valuable despite no empirical support and no examination of the foundational assumptions regarding the validity of human memory and retrospective recall in dietary assessment. We assert that uncritical faith in the validity and value of M-BMs has wasted substantial resources and constitutes the greatest impediment to scientific progress in obesity and nutrition research. Herein, we present evidence that M-BMs are fundamentally and fatally flawed owing to well-established scientific facts and analytic truths. First, the assumption that human memory can provide accurate or precise reproductions of past ingestive behavior is indisputably false. Second, M-BMs require participants to submit to protocols that mimic procedures known to induce false recall. Third, the subjective (ie, not publicly accessible) mental phenomena (ie, memories) from which M-BM data are derived cannot be independently observed, quantified, or falsified; as such, these data are pseudoscientific and inadmissible in scientific research. Fourth, the failure to objectively measure physical activity in analyses renders inferences regarding diet-health relationships equivocal. Given the overwhelming evidence in support of our position, we conclude that M-BM data cannot be used to inform national dietary guidelines and that the continued funding of M-BMs constitutes an unscientific and major misuse of research resources.
Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
... Today most diets are supplemented with niacin through enriched flour, which receives its name because of the added niacin. 13 Niacin can be administered in doses of 2g to 4g to causes a decrease in circulating levels of cholesterol and LDL. While the cholesterol lowering effects of niacin are desirable there are potential side effects from such large doses of this vitamin. ...
This manuscript describes the lecture on vitamins contained in the core course entitled, "The Biochemical Basis of Drugs and Diseases" (Pharmacy 3050). In the first year, our curriculum is designed to focus on systems and diseases. As such, this course acts in concert with both the Anatomy & Physiology course and the Pathophysiology course to present an integrated view of human diseases and systems. The second year of our curriculum is focused on learning about drugs classes and the mechanism of action. The third year of the curriculum is focused on simulated patients, while the forth year of the curriculum the students are presented with real patients. The lecture on vitamins is the last topic of a course focused primarily on metabolism. Because many vitamins play major roles in metabolic cycles, this lecture allows for a brief review of much of the material covered throughout the course. Therefore, vitamin examples are primarily chosen to reinforce major metabolic cycles and also their role in human disease. There is more clinical information that is relevant to vitamins than what is presented in this lecture. However, since first year students in our curriculum have almost no knowledge of therapeutics, the focus of the lecture is on diseases and not clinical practice.
... Then, in the period from 1906 to 1940, it reached epidemic proportions, resulting in more than 3 million cases and 100,000 deaths (2). Cases were most predominant among the socially disadvantaged: almost always among the very poor and disproportionately among blacks and women (3,4). ...
As pellagra reached epidemic proportions in the United States in the early 20th century, 2 teams of investigators assessed
its incidence in cotton mill villages in South Carolina. The first, the Thompson-McFadden Commission, concluded that pellagra
was likely infectious. The second, a Public Health Service investigation led by Joseph Goldberger, concluded that pellagra
was caused by a dietary deficiency. In this paper, we recount the history of the 2 investigations and consider how the differences
between the 2 studies' designs, measurements, analyses, and interpretations led to different conclusions. Because the novel
dietary assessment strategy was a key feature of the Public Health Service's study design, we incorporated simulated measurement
error in a reanalysis of the Public Health Service's data to assess whether this specific difference affected the divergent
conclusions.
... longer required once it was realised that it was due to a deficiency in niacin (nicotinic acid, vitamin B3) or the amino acid tryptophan from which niacin can be derived. Pellagra was relatively easy to treat once the diagnosis was established, so basic science research aimed at unravelling the mechanism was unnecessary (32). ...
Photosensitivity disorders are caused by a variety of mechanisms. Three common themes are as follows: excess chromophore allowing visible light energy to cause photodynamic damage; reduced DNA repair capacity to UV-induced DNA damage; enhanced sensitivity to light-induced allergens mediated immunologically. Although the cause of each condition may be known, the precise pathogenesis underlying the photosensitivity has taken longer to understand. By focussing on three clinical disorders under each of these themes we have explored the following: why erythropoeitic protoporphyria differs so markedly from the other cutaneous porphyrias; how a DNA repair defect was eventually revealed to be the underlying cause of the vitamin B3 deficiency disorder of pellagra; an immunological explanation for the over reactivity to photoallergens in chronic actinic dermatitis. This article is protected by copyright. All rights reserved.
... Pellagra was not a public health problem in other parts of the world, perhaps because they had a more varied diet that provided sufficient amounts of niacin. 19 ...
Maize (Zea mays), also called corn, is believed to have originated in central Mexico 7000 years ago from a wild grass, and Native Americans transformed maize into a better source of food. Maize contains approximately 72% starch, 10% protein, and 4% fat, supplying an energy density of 365 Kcal/100 g and is grown throughout the world, with the United States, China, and Brazil being the top three maize-producing countries in the world, producing approximately 563 of the 717 million metric tons/year. Maize can be processed into a variety of food and industrial products, including starch, sweeteners, oil, beverages, glue, industrial alcohol, and fuel ethanol. In the last 10 years, the use of maize for fuel production significantly increased, accounting for approximately 40% of the maize production in the United States. As the ethanol industry absorbs a larger share of the maize crop, higher prices for maize will intensify demand competition and could affect maize prices for animal and human consumption. Low production costs, along with the high consumption of maize flour and cornmeal, especially where micronutrient deficiencies are common public health problems, make this food staple an ideal food vehicle for fortification.
... Curiously enough, despite their staple diet of maize, populations of Mexico and Central America have remained essentially pellagra-free. This is probably due to the traditional method of preparation of maize by presoaking it in lime before cooking (nixtamalization) which improves the bioavailability of calcium and liberates part of the bound niacin, enhancing the dietary content of niacin and ensuring protection against pellagra if eaten regularly in the absence of legumes or animal protein (Rajakumar 2000). The causes and cure of pellagra were discovered, not in the Mediterranean, but by Dr. ...
Abstract
Heywood, V.H.: The role of New World biodiversity in the transformation of Mediterranean
landscapes and culture. — Bocconea 24: 69-93. 2012. — ISSN 1120-4060.
Over the past two millennia the Mediterranean region has been the recipient of many waves of
plant introductions, some of which have produced major effects on the landscapes and lives of
the peoples who inhabit its shores. The impacts of the introductions made by the Romans and
the Moors are compared with those of the ‘Columbian exchange’ which led to a systematic and
massive transfer and diffusion of plants, animals and diseases between the old and new worlds.
The effects of the various introductions on both agricultural and urban landscapes are discussed
as are the impacts on human diet and nutrition which had important demographic consequences
and both deleterious effects on human health as well as providing plant-based medicines to cure
some diseases such as malaria. Some of these effects are still being played out today. The social
and economic consequences, although initially, scarcely perceptible, were quite profound in the
subsequent centuries after the initial introductions. The landscapes and the economy of the
region have also been affected in more recent times by changes in the way that the introduced
crops are cultivated, such as intensification including irrigation and cultivation of fruit, salad
crops and flowers in greenhouses or under plastic, crop substitutions such as sunflower
(Helianthus) for olive, increased reforestation and plantation forests, often with exotic species
such as Eucalyptus. Urban landscapes have been transformed as a consequence of the widespread
introduction of ornamental subtropical species that are now almost their defining features.
Finally, invasive alien species are an increasing threat to landscapes in several
Mediterranean countries and likely to become more widespread in the face of climate change.
Vit B3, also known as niacin or nicotinic acid, is a water-soluble member of the Vit B3 complex, a family of vitamins that includes nicotinamide and nicotinamide riboside. Niacin was first described by chemist Hugo Weidel in his studies of nicotine [1]. It was later extracted from liver tissue by biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then referred to as the “pellagra-preventing factor” and the “anti-blacktongue factor.” [2] Nowadays, niacin is referred to as Vit B3 because it was the third of the B vitamins to be discovered. Niacin cannot be directly converted to nicotinamide, but since both compounds are precursors of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in vivo, the term Vit B3 is used as a blanket term for both [3].
In recent years, the fundamental variety and biological influence of pyridine and its derivatives make them fascinating aims for preparation. These versatile compounds can be found in several bioactive natural products, drugs, functional materials and have been known as important chemical and pharmaceutical agents. As a result, the synthesis of pyridines remains an attractive subject to industrial and synthetic chemists. Based on the aforementioned properties, in this chapter, the recent advances in the catalytic synthesis of pyridine and its derivatives are collected. Several heterogeneous and homogeneous catalytic methods such as acidic and basic catalysts, nanocatalysis, ionic liquids, and molten salts, supported catalysts, transition metal catalysis, organocatalysts, I2, etc. have been employed for the synthesis of pyridines. Furthermore, these interesting compounds were constructed by numerous protocols such as metal-free catalysis, classical heating, sonication, and microwave irradiation by using solvents or solvent-free conditions. Also, this chapter highlights regioselectivity, isolated yields, and reaction conditions for the catalytic synthesis of pyridine derivatives.
We develop a data-driven method for linking people in cities over time that can be used in any country that has data tracking the locations of individuals across multiple periods. We apply this process to United States Census data from 1900 through 1940 and find that, of the 1,000 largest cities in 1900, 15 percent experienced a decline in population by 1940. We also use the large data set for this same time period, linking more than 45 million people across adjacent census records to examine which types of people exit a shrinking city and how their eventual socioeconomic outcomes differ from those who stay. Nationally, we find that those who left shrinking cities had longer life spans, greater income, better jobs, and higher education than those who stayed. We note that the regional analyses tend to follow the positive national pattern while indicating the geographic place-based differences of the cities that lost population. We also show the relation of race to the tendency to migrate from different types of cities. This method for linking millions of individuals across censuses has the potential to reveal other important characteristics of past populations, such as multidecade migration patterns and household changes in various regions over time.
Pyridine (py) is an important heterocyclic compound and is an integral part of various natural products. There are various medicines containing py ring system being available in the market to combat different human ailments. Observing the medicine market, Omeprazole, a widely used py‐based drug in medicinal market since 1998. Netupitant (an antiemitic drug, since 2014) is used in combination with another drug to prevent acute and delayed vomiting and nausea associated with cancer chemotherapy led the run towards development of anticancer drugs. Several drugs have been approved by FDA for the treatment of cancer in recent years such as, Abemaciclib (2015), Lorlatinib (2018), Apalutamide (2018) and Ivosidenib (2019). Research on py on the bases of these advancements is an evergreen field and associated with greater hopes to address several disease related issues. Several compounds are in the process of clinical trials and are expected to serve various purposes in days to come. This review article deals with recent findings in py chemistry and its coordination complexes. The medicinal efficiency has been argued for organic and inorganic derivatives. Selected biological applications are hereby discussed as follow up study of our report in 2015. Suitable literature prior to 2015 has also been incorporated in appropriate places in order to cover the scope in broader sense. Pyridine, an important heterocyclic compound is part of various medicines to combat different human ailments. Omeprazole, Netupitant, Abemaciclib, Ivosidenib, Lorlatinib and Apalutamide have been approved by FDA, several compounds are in the process of clinical trials. Selected biological applications in the field of medicine are hereby discussed.
Objective
Pellagra is a nutritional deficiency disease associated with niacin (vitamin B3) deficiency. The history of pellagra is well documented for Europe and the USA, but less is known about the prevalence in sub-Saharan African countries. This study documents the history of pellagra in South Africa, as diagnosed based on dermatological symptoms.
Design
Narrative review of information from scientific databases, library archives, other archives and record services and from Statistics South Africa.
Setting
South Africa, 1897-2019.
Participants
South African
Results
Pellagra was first officially recorded in South Africa in 1906, but there are earlier indications of the disease. The prevalence of pellagra peaked after it was all but eradicated in the USA and Europe. Pellagra was never as prevalent in South Africa as in Europe, the USA and Egypt, where special hospitals for pellagrins were established. However, studies on urinary excretion of metabolites conducted in 1960s and 1970s suggested a high prevalence of subclinical (sub-pellagra) niacin deficiency, especially in previously disadvantaged Black populations. As in Europe and the USA, pellagra was associated with poverty and an overdependence on maize as staple food. Malnutrition was the main cause of the disease, but alcohol abuse might have been a contributing factor. In South Africa, reports of pellagra had declined by the late 1980s/early 1990s, and hardly any cases were reported by the year 2000.
Conclusions
Although pellagra, diagnosed based on dermatological symptoms, appears to be largely eradicated in South Africa, it does not rule out the potential for subclinical niacin deficiency.
References: Brickley, M.B. Ives, R. & Mays, S. (2020). The Bioarchaeology of Metabolic Bone Disease, Second Edition
Dihydronicotinamide riboside (NRH) has been suggested to act as a precursor for the synthesis of NAD⁺, but the biochemical pathway converting it has been unknown. Here, we show that NRH can be converted into NAD⁺ via a salvage pathway in which adenosine kinase (ADK, also known as AK) acts as an NRH kinase. Using isotope-labelling approaches, we demonstrate that NRH is fully incorporated into NAD⁺, with NMNH acting as an intermediate. We further show that AK is enriched in fractions from cell lysates with NRH kinase activity, and that AK can convert NRH into NAD⁺. In cultured cells and mouse liver, pharmacological or genetic inhibition of AK blocks formation of reduced nicotinamide mononucleotide (NMNH) and inhibits NRH-stimulated NAD⁺ biosynthesis. Finally, we confirm the presence of endogenous NRH in the liver with metabolomics. Our findings establish NRH as a natural precursor of NAD⁺ and reveal a new route for NAD⁺ biosynthesis via an NRH salvage pathway involving AK.
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite involved in various cellular processes. The cellular NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human. NAD+ metabolism is an emerging therapeutic target for several human disorders including diabetes, cancer, and neuron degeneration. Factors regulating NAD+ homeostasis have remained incompletely understood due to the dynamic nature and complexity of NAD+ metabolism. Recent studies using the genetically tractable budding yeast Saccharomyces cerevisiae have identified novel NAD+ homeostasis factors. These findings help provide a molecular basis for how may NAD+ and NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function. Here we summarize major NAD+ biosynthesis pathways, selected cellular processes that closely connect with and contribute to NAD+ homeostasis, and regulation of NAD+ metabolism by nutrient-sensing signaling pathways. We also extend the discussions to include possible implications of NAD+ homeostasis factors in human disorders. Understanding the cross-regulation and interconnections of NAD+ precursors and associated cellular pathways will help elucidate the mechanisms of the complex regulation of NAD+ homeostasis. These studies may also contribute to the development of effective NAD+-based therapeutic strategies specific for different types of NAD+ deficiency related disorders.
Controversies regarding the putative health effects of dietary sugar, salt, fat, and cholesterol are not driven by legitimate differences in scientific inference from valid evidence, but by a fictional discourse on diet-disease relations driven by decades of deeply flawed and demonstrably misleading epidemiologic research. Over the past 60 years, epidemiologists published tens of thousands of reports asserting that dietary intake was a major contributing factor to chronic non-communicable diseases despite the fact that epidemiologic methods do not measure dietary intake. In lieu of measuring actual dietary intake, epidemiologists collected millions of unverified verbal and textual reports of memories of perceptions of dietary intake. Given that actual dietary intake and reported memories of perceptions of intake are not in the same ontological category, epidemiologists committed the logical fallacy of ‘Misplaced Concreteness’. This error was exacerbated when the anecdotal (self-reported) data were impermissibly transformed (i.e., pseudo-quantified) into proxy-estimates of nutrient and caloric consumption via the assignment of ‘reference’ values from databases of questionable validity and comprehensiveness. These errors were further compounded when statistical analyses of diet-disease relations were performed using the pseudo-quantified anecdotal data. These fatal measurement, analytic, and inferential flaws were obscured when epidemiologists failed to cite decades of research demonstrating that the proxy-estimates they created were often physiologically implausible (i.e., meaningless) and had no verifiable quantitative relation to the actual nutrient or caloric consumption of participants. In this critical analysis, we present substantial evidence to support our contention that current controversies and public confusion regarding diet-disease relations were generated by tens of thousands of deeply flawed, demonstrably misleading, and pseudoscientific epidemiologic reports. We challenge the field of nutrition to regain lost credibility by acknowledging the empirical and theoretical refutations of their memory-based methods and ensure that rigorous (objective) scientific methods are used to study the role of diet in chronic disease.
Pellagra is characterised by dermatological, gastrointestinal and neuropsychiatric manifestations. Millions contracted the disease and hundreds of thousands died between the time it was first recorded until pellagra was finally recognised as a niacin-deficiency disease. Pellagra became epidemic when maize, with its limited bio-availability of nutrients such as niacin and tryptophan, became the staple food in the near-monophagic diets of the impoverished and institutionalised. By the mid-20th century, pellagra was all but eradicated in large parts. The decline in prevalence can largely be ascribed to a better understanding of the link between nutrition and disease, improvements in socio-economic conditions of workers and food enrichment. We briefly review aetiological doctrines on pellagra and the global spread of the disease from the early 18th century until the middle of the 20th century. In the final analysis, we examine the reasons for, and the legitimacy of, the persistent association between pellagra and the consumption of maize.
Significance:
• Almost two centuries have elapsed since the first description of pellagra and its general acceptance as a nutritional-deficiency disease.
• The link between maize and pellagra is primarily a reflection of the nutritional inadequacies of a near monophagic diet over-dependent on a grain deficient in bioavailable niacin and tryptophan.
• We refute the concept of nixtamalisation as the main reason for the apparent absence of pellagra in early pre-Columbian North American, Mesoamerican and South American cultures.
Nicotinamide adenine dinucleotide (NAD+) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD+ is required for the activity of multifunctional enzymes including sirtuins and poly(ADP-ribose) polymerases (PARPs) that regulate post-translational modifications, DNA damage responses, and calcium signaling. Recent research indicates that NAD+ participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+ precursors including nicotinamide riboside (NR) that boost or replete the NAD+ metabolome may be cardioprotective. This review examines the molecular physiology and preclinical data with respect to NAD+ precursors in heart failure related cardiac remodeling, ischemic/reperfusion injury, and arrhythmias. In addition, alternative NAD+ boosting-strategies and potential systemic effects of NAD+ supplementation with implications on cardiovascular health and disease are surveyed.
Pellagra is a deficiency of niacin or its amino acid precursor, tryptophan, which presents with the classic four Ds: the characteristic dermatitis, diarrhea, dementia, and eventually death if left untreated. The incidence of pellagra is quite rare presently because of increased awareness and strategies such as vitamin fortification. However, the deficiency is still present in cultures that rely on maize as their primary source of sustenance. We report a recent outbreak in a catchment area in Kasese, Malawi, of 691 cases of pellagra which were successfully treated with niacin supplementation. We present this short report to highlight the importance of educating providers of at-risk populations about this diagnosis and to consider solutions for these populations to prevent further deficiencies.
The field of public health has a long, successful history of health promotion and disease prevention, including efforts relevant to mental health problems. Recent years have been marked by a dramatic increase in the development, implementation, and assessment of approaches to prevent the incidence of mental disorders. This chapter examines the rationale for prevention, the theories and methods that inform prevention science, the prevention strategies being employed across developmental stages and at multiple ecological levels, and emerging directions for the prevention field.
This position paper developed the argument that creating innovative and forward-thinking conceptual approaches to consumer education is a proactive process, the trademark of consumer activism. Assuming that (re)conceptualizing consumer education is a form of consumer activism, this paper identified the conceptual contributions and intellectual innovations of 24 consumer education initiatives in North America (1962-2012). Using an historical analysis method, this study profiled consumer educators who tried to stay ahead of the curve by creating leading-edge approaches to socializing people into their consumer role. In effect, they were expressing their personal and intellectual convictions about the potential and possibilities of consumer education as a means to promote change in order to protect and empower people in their consumer-citizen role. This article is protected by copyright. All rights reserved.
The phenomenon of cities facing dramatic population loss, the so-called ‘shrinking city’, offers new challenges for urban scholars. After decades of focusing on growth, geographers, planners, politicians, and others are now confronted with cities and regions that are not just losing people, but often also facing economic and social transformation. As an area of study, we are in the beginning stages of theorizing new urban futures for these cities, as well as developing local planning responses to them.
Resumen. El fenómeno de las ciudades que se enfrentan a una pérdida drástica de población, llamadas también “ciudades menguantes”, ofrece nuevos retos para quienes investigan el urbanismo. Después de décadas de preocuparse por el crecimiento, los geógrafos, planificadores, políticos y otros se enfrentan ahora a ciudades y regiones que no sólo están perdiendo su población, sino que a menudo también se enfrentan a transformaciones económicas y sociales. Como área de estudio, nos encontramos en las etapas iniciales de la elaboración de teorías sobre los nuevos futuros urbanos de estas ciudades, así como del desarrollo de respuestas de planificación local para las mismas.
Wound healing is a complex process that is influenced by multiple systemic factors, including nutritional status. While nutritional support is commonly recognized as an important aspect of comprehensive wound management, the focus is typically on replacement of macronutrients, specifically calories and protein. Our experience strongly suggests that micronutrients are equally important, that micronutrient deficiencies are common, and that correction of these deficiencies frequently leads to wound healing when incorporated into a comprehensive wound management program. This article provides guidelines for assessment and management of micronutrient deficiencies.
The ability to make strong causal inferences, based on data derived from outside of the laboratory, is largely restricted to data arising from well-designed randomized control trials. Nonetheless, a number of methods have been developed to improve our ability to make valid causal inferences from data arising from observational studies. In this paper, I review concepts of causation as a background to counterfactual causal ideas; the latter ideas are central to much of current causal theory. Confounding greatly constrains causal inferences in all observational studies. Confounding is a biased measure of effect that results when one or more variables, that are both antecedent to the exposure and associated with the outcome, are differentially distributed between the exposed and non-exposed groups. Historically, the most common approach to control confounding has been multivariable modeling; however, the limitations of this approach are discussed. My suggestions for improving causal inferences include asking better questions (relates to counterfactual ideas and "thought" trials); improving study design through the use of forward projection; and using propensity scores to identify potential confounders and enhance exchangeability, prior to seeing the outcome data. If time-dependent confounders are present (as they are in many longitudinal studies), more-advanced methods such as marginal structural models need to be implemented. Tutorials and examples are cited where possible.
The First Progress Report of the Thompson-McFadden Pellagra Commission was published in successive numbers of the American Journal of the Medical Sciences from April to September in 1913, and a summary of this material appeared in The Journal of the American Medical Association, Jan. 3, 1914. The chief conclusions from the first year's work were stated as follows:
• The supposition that the ingestion of good or spoiled maize is the essential cause of pellagra is not supported by our study.
• Pellagra is in all probability a specific infectious disease communicable from person to person by means at present unknown.
• We have discovered no evidence incriminating flies of the genus Simulium in the causation of pellagra, except their universal distribution throughout the area studied. If it is distributed by a blood-sucking insect, Stomoxys calcitrans would appear to be the most probable carrier.
• We are inclined to regard intimate association in the
At the Twenty-eighth Annual Meeting of the American Public Health Association,1 held in Indianapolis, Ind., Oct. 22-26, 1900, we presented, in the form of a preliminary note, the results of our bacteriologic study of yellow fever, based on cultures taken from the blood in eighteen cases, at various stages of the disease, as well as on those which we had made from the blood and organs of eleven yellow fever cadavers. We also recorded the results obtained from the inoculation of eleven non-immune individuals by means of the bite of mosquitoes (culex fasciatus, Fabr.) that had previously fed on the blood of patients sick with yellow fever. We were able to report two positive results, in which the attack of yellow fever followed the bite of a mosquito within the usual period of incubation of this disease.
In one of these cases all other sources of infection could be positively
Yellow fever was a disease of unknown cause, curious, almost haphazard spread, short duration, and, often, a high fatality rate. It died out soon after a frost and did not appear in cool climates or high elevations. Some thought filth caused its spread — that it arose in the fetid, reeking decay around docks. Others believed it to be imported, mainly by ships from tropical lands. It rarely attacked nurses, doctors, or hospital attendants. The very mystery increased the sickening fear it created. It brought business to a halt. People fled from it if they could. Thus, when the manner of its spread was learned and could be stopped, it was stripped of its lethal secrets. We today who go careless and carefree are a forgetful people.The article reprinted in this issue of The Journal
The practice of making white flour by the process of roller milling was introduced about 1870. Although the texture and color of the white flour produced by this method was a great improvement over the gray, coarse, stone-ground flour, the more refined white flour contained much less of the coatings of the wheat grain and thus less vitamins and minerals. As a result of this process of milling and other changes in the preparation of our food, the amount of thiamine (vitamin B1) and other so-called micronutrients was reduced in the American diet. From the first, there were critics of the roller-milling process, but after McCollum and Osborne and Mendel revealed the importance to health of these vitamins in the later 1910's, the flour millers and commercial bakers were under constant fire from physicians and nutritionists.
Reliable surveys of the nutritional condition of the people revealed that the average
The evidence now available abundantly demonstrates that pellagra is a manifestation of dietary deficiency. Exactly what dietary factor or factors are concerned, however, is not so clear, although the indications have for some time increasingly pointed to the protein,1 that is, to some amino-acid deficiency, as the essential primary factor concerned in the causation of the disease.In support of this interpretation, we reported2 last spring the recurrence of pellagra in five patients in spite of a daily consumption, during periods of not less than two and one-half months before the appearance of the distinctive eruption, of a diet presumably adequately supplied with both minerals and known vitamins, thus tending to exclude these and pointing to amino-acid deficiency as the essential factor. Since that report was written, we have been able to make some additional observations that point even more strongly to amino-acid deficiency as the primary etiologic
This is a section of the book The Challenge of Epidemiology: Issues and Selected Readings. Edited by four eminent epidemiologists, this book consolidates, for the first time, a core of landmark articles on the evolution, scope and limitations, uses, and prospects of epidemiology. An outstanding feature of the book is the inclusion of the editors' assessments of the realm of epidemiology, where it is and where it should be going. It represents a useful tool for both students and practicing professionals and provides a much-needed frame of reference for reorienting the practice of epidemiology. The book is a collection of 91 articles, grouped in five parts. This article presents a study on the relation of economic conditions (income and others) to the prevalence and incidence of pellagra in cotton-mill villages of South Carolina in 1916. A detailed examination of the villages, as well as a comparison of incidences between villages and household, is discussed in the article.
The epidemic of pellagra in the first half of this century at its peak produced at least 250,000 cases and caused 7,000 deaths a year for several decades in 15 southern states. It also filled hospital wards in other states, which had a similar incidence but refused to report their cases. Political influences interfered, not only with surveillance of the disease, but also in its study, recognition of its cause, and the institution of preventive measures when they became known. Politicians and the general public felt that it was more acceptable for pellagra to be infectious than for it to be a form of malnutrition, a result of poverty and thus an embarrassing social problem. Retrospectively, a change in the method of milling cornmeal, degermination, which began shortly after 1900, probably accounted for the appearance of the epidemic; such a process was suggested at the time, but the suggestion was ignored.
Francois Thiery and pellagra
- Rh Major
- Gasper
Major RH: Don Gasper Casal, Francois Thiery and pellagra. Bull Hist Med 1944; 16:351-361
Ankylostomiasis in an individual presenting all of the typical symptoms of pellagra
- Hf Harris
Harris HF: Ankylostomiasis in an individual presenting all
of the typical symptoms of pellagra. Am Med 1902; 4:99-100
A note on the history of pellagra in the United States
- Ga Wheeler
Wheeler GA: A note on the history of pellagra in the
United States. Public Health Rep 1931; 46:2223-2229
Agricultural aspects of the pellagra problem in the United States
- Cl Alsberg
Alsberg CL: Agricultural aspects of the pellagra problem in
the United States. N Y Med J 1909; 90:50-54
Pellagraphobia: a word of caution
- Gm Niles
Niles GM: Pellagraphobia: a word of caution. JAMA 1912;
58:1341-1342
The treatment of pellagra by autoserotherapy
- Ee Palmer
- Wl Secor
Palmer EE, Secor WL: The treatment of pellagra by
autoserotherapy. JAMA 1915; 64:1566-1567
The prevalence and geographic distribution of pellagra in the United States
- Ch Lavinder
Lavinder CH: The prevalence and geographic distribution
of pellagra in the United States. Public Health Rep 1912;
27:2076-2088
Attempts to transmit pellagra to monkeys
- Ch Lavinder
- E Francis
- Rm Grimm
Lavinder CH, Francis E, Grimm RM, et al: Attempts to
transmit pellagra to monkeys. JAMA 1914; 63:1093-1094
The etiology of pellagra. the significance of certain epidemiological observations with respect thereto
- J Goldberger
Goldberger J: The etiology of pellagra. the significance of
certain epidemiological observations with respect thereto.
Public Health Rep 1914; 29:1683-1686
Pellagra in the Mississippi flood area
- J Goldberger
- E Sydenstricker
Goldberger J, Sydenstricker E: Pellagra in the Mississippi
flood area. Public Health Rep 1927; 42:2706-2725
The history of pellagra, its recognition as a disorder of nutrition and its conquest Recommended Reading Etheridge FW: The Butterfly Caste. A Social History of Pellagra in the South Roe DA: A Plague of Corn. The Social History of Pellagra
- Sydenstricker
Sydenstricker VP: The history of pellagra, its recognition as a disorder of nutrition and its conquest. Am J Clin Nutr 1958; 6:409-414 Recommended Reading Etheridge FW: The Butterfly Caste. A Social History of Pellagra in the South. Westport, Conn, Greenwood Publishing Co, 1972 Roe DA: A Plague of Corn. The Social History of Pellagra. Ithaca, NY, Cornell University Press, 1973
Society proceedings. conference on pellagra
Society proceedings. conference on pellagra. JAMA 1909;
53:1659-1670
- Ws Hall
- James Woods Psychiatrist
- Md Babcock
Hall WS: Psychiatrist, humanitarian and scholar James
Woods Babcock, MD. J SC Med Assoc 1970; 66:366-371
Essays on History of Nutrition and Dietetics
- J Goldberger
- Pellagra
Goldberger J: Pellagra. Essays on History of Nutrition and
Dietetics. Chicago, American Dietetic Association, 1967, pp
103-106
An epidemic of acute pellagra. Transactions of the Medical Association of Alabama
- Gh Searcy
Searcy GH: An epidemic of acute pellagra. Transactions of
the Medical Association of Alabama, 1907, pp 387-393
The prevention of pellagra. a test of diet among institutional inmates
- J Goldberger
- Ch Waring
- Dg Willets
Goldberger J, Waring CH, Willets DG: The prevention of
pellagra. a test of diet among institutional inmates. Public
Health Rep 1915; 30:3117-3131