Pellagra Research Articles

Nutritional Factors That Affect the Formation of 5-Aminolevulinic Acid, a Key Intermediate of Heme Biosynthesis.

5-Aminolevulinic acid (ALA) is a key intermediate of heme biosynthesis, which is an essential component of the respiratory chain. Therefore, nutrients that affect ALA biosynthesis eventually affect ATP production, which is the basis of mitochondrial function. Although the effects of various non-nutrient components that affect ALA after biosynthesis have been reported, there are few reports on the effects of dietary amino acids/protein on ALA formation and the effects of dietary vitamins that are involved in amino acid metabolism. In mitochondria, ALA is synthesized from succinyl-CoA and glycine by the pyridoxal phosphate-dependent enzyme ALA synthase [EC 2.3.1.37]. In this study, the effects of dietary amino acids/protein and vitamins on the amount of ALA synthesized were investigated using mice, rats, and cultured cells. Amounts of ALA in plasma and urine, and porphyrins in plasma increased with increasing protein intake. Vitamin B1 insufficiency did not affect ALA synthesis. Vitamin B6 insufficiency increased the amount of ALA synthesized, while niacin deficiency markedly reduced ALA synthesis. Thus, for heme synthesis, an essential biological substance for life, the amounts of amino acids, as well as the pathways metabolizing amino acids to glycine and succinyl-CoA are very important. Specifically, it is important that niacin is associated with the formation of glycine and succinyl-CoA from amino acids.

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation.

Vitamin B3 (nicotinic acid, niacin) deficiency causes the systemic disease pellagra, which leads to dermatitis, diarrhea, dementia, and possibly death depending on its severity and duration. Vitamin B3 is used in the synthesis of the NAD+ family of coenzymes, contributing to cellular energy metabolism and defense systems. Although nicotinamide (niacinamide) is primarily used as a nutritional supplement for vitamin B3, its pharmaceutical and cosmeceutical uses have been extensively explored. In this review, we discuss the biological activities and cosmeceutical properties of nicotinamide in consideration of its metabolic pathways. Supplementation of nicotinamide restores cellular NAD+ pool and mitochondrial energetics, attenuates oxidative stress and inflammatory response, enhances extracellular matrix and skin barrier, and inhibits the pigmentation process in the skin. Topical treatment of nicotinamide, alone or in combination with other active ingredients, reduces the progression of skin aging and hyperpigmentation in clinical trials. Topically applied nicotinamide is well tolerated by the skin. Currently, there is no convincing evidence that nicotinamide has specific molecular targets for controlling skin aging and pigmentation. This substance is presumed to contribute to maintaining skin homeostasis by regulating the redox status of cells along with various metabolites produced from it. Thus, it is suggested that nicotinamide will be useful as a cosmeceutical ingredient to attenuate skin aging and hyperpigmentation, especially in the elderly or patients with reduced NAD+ pool in the skin due to internal or external stressors.

GD03: Pellagra in low‐income settings: can we prevent it?

GD03: Pellagra in low‐income settings: can we prevent it?

Syndrome multicarentiel catastrophique post bypass gastrique

IntroductionBariatric surgery is a very effective treatment for obesity. After gastric bypass, micronutrient deficiencies frequently occur which can have dramatic consequences. Case reportWe report the case of a 55-year-old woman who was admitted for psychomotor retardation, bilateral leg pitting edema and psoriasis-like rash that had been ongoing for 3 months. Pancytopenia, encephalopathy and heart failure rapidly occurred leading to multiorgan dysfunction syndrome and death. We retrospectively identified severe selenium deficiency with possible secondary cardiomyopathy, niacin deficiency resulting in pellagrous encephalopathy with skin lesions and gelatinous transformation of bone marrow. ConclusionMicronutrient deficiency should systematically be assessed when new symptoms occur in a patient with a history of bariatric surgery. Selenium deficiency should be considered in the presence of any heart failure in this context.

Identification of protein related to dietary vitamin B3 deficiency in Mediterranean fruit fly larvae.

Mediterranean fruit fly (medfly), Ceratitis capitata, is among the most destructive agricultural pest. The sterile insect technique (SIT) can effectively control medfly populations. To rear healthy medflies for the purpose of SIT, it is essential to supplement B vitamins in the diet. However, the function of the dietary B vitamins in C. capitata larvae is not known. With the microscopic analysis, several organs in the head were examined and the spiracle formation and sensory organs were normally formed between the niacin-supplied and niacin-absent groups. However, formation of the ocular depression was differently developed between the two groups, although the hypostomal sclerite was formed properly. These results signify that niacin deficiency maybe interrupt development of medfly larvae ocular depression. Proteomic analyses using LC MS/MS detected a total of 1845 proteins in two flies. A total of 607 of the 1845 proteins were overexpressed and one third (598 proteins) were downexpressed in the niacin-deficient larvae, while about one third were similarly expressed. Overexpressed proteins in the niacin-deficient larvae included ryanodine receptor 44 F, intergrin-PS, spalt-major homeotic protein, and chiffon protein. One of important overexpressed proteins was optomotor-blind protein in relation to wing development in the niacin-deficient medfly larvae.

The use of Neurobion Forte in the Treatment of Pellagra in an adult on anti-TB treatment: A case report from Lusaka, Zambia

The deficiency of Niacin and/or its precursor amino acid, Tryptophan can result in a disease called Pellagra. Isoniazid (INH), a key drug used in tuberculosis (TB) treatment has been associated with pellagra particularly in developing nations where poor nutritional status is highly prevalent among its people.We report a case of pellagra with classical dermatological manifestations (hyperpigmented skin lesions around the neck), on the face, and external surfaces of the upper limbs) in a black African HIV negative adult female, on TB treatment for 11 weeks managed with a combo of Vitamin B1 - 10mg, Vitamin B2 - 10mg, Vitamin B3 - 45mg, Vitamin B5 - 50mg, Vitamin B6 - 3mg and ® Vitamin B12 - 15mcg (Neurobion Forte) with noticeable response to the treatment within one week.

The use of Neurobion® Forte in the Treatment of Pellagra in an adult on anti-TB treatment: A case report from Lusaka, Zambia

Abstract
 The deficiency of Niacin and/or its precursor amino acid, Tryptophan can result in a disease called Pellagra. Isoniazid (INH), a key drug used in tuberculosis (TB) treatment has been associated with pellagra particularly in developing nations where poor nutritional status is highly prevalent among its people.We report a case of pellagra with classical dermatological manifestations (hyperpigmented skin lesions around the neck), on the face, and external surfaces of the upper limbs) in a black African HIV negative adult female, on TB treatment for 11 weeks managed with a combo of Vitamin B1 - 10mg, Vitamin B2 - 10mg, Vitamin B3 - 45mg, Vitamin B5 - 50mg, Vitamin B6 - 3mg and Vitamin B12 - 15mcg (Neurobion® Forte) with noticeable response to the treatment within one week.

Pellagra in South Africa from 1897 to 2019: a scoping review.

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. Scoping review of information from scientific databases, library archives, other archives and record services and from Statistics South Africa. South Africa, 1897-2019. South African. 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. 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.

Hidden in the Rash - Alcoholic Pellagra Encephalopathy

Pellagra Encephalopathy is a recognised medical condition due to niacin deficiency. Patients with alcohol dependence invariably have vitamin deficiencies, including niacin. Pellagra Encephalopathy can be challenging to diagnose alongside withdrawal delirium. Diarrhoea, skin rashes, memory and attention deficits, paraesthesia and proximal muscle weakness were noted in four patients diagnosed with delirium tremens. Atypical features such as cognitive and neurological deficits were understood as the presentation of pellagra encephalopathy. The presence of neuro-cognitive symptoms in addition to typical dermatological presentation guided consideration of pellagra encephalopathy comorbid with delirium due to alcohol withdrawal. Subtle neurological symptoms indicative of pellagra encephalopathy may be overlooked in patients with delirium.

Pellagra a review exploring causes and mechanisms, including isoniazid-induced pellagra.

Pellagra is a clinical syndrome caused by a deficiency of niacin (nicotinic acid) and/or its precursor tryptophan. The cardinal manifestations are 4 D's: dermatitis, diarrhoea, dementia and in worst case death. Increased use of isoniazid prophylaxis along with antiretroviral therapy in countries where latent tuberculosis is common has been associated with increased presentations with pellagra.

Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson's Disease.

Dysbiosis is implicated by many studies in the pathogenesis of Parkinson’s disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.

Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi.

Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi.Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3–25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim.Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.

ACE2 and gut amino acid transport.

ACE2 is a type I membrane protein with extracellular carboxypeptidase activity displaying a broad tissue distribution with highest expression levels at the brush border membrane (BBM) of small intestine enterocytes and a lower expression in stomach and colon. In small intestinal mucosa, ACE2 mRNA expression appears to increase with age and to display higher levels in patients taking ACE-inhibitors (ACE-I). There, ACE2 protein heterodimerizes with the neutral amino acid transporter Broad neutral Amino acid Transporter 1 (B0AT1) (SLC6A19) or the imino acid transporter Sodium-dependent Imino Transporter 1 (SIT1) (SLC6A20), associations that are required for the surface expression of these transport proteins. These heterodimers can form quaternary structures able to function as binding sites for SARS-CoV-2 spike glycoproteins. The heterodimerization of the carboxypeptidase ACE2 with B0AT1 is suggested to favor the direct supply of substrate amino acids to the transporter, but whether this association impacts the ability of ACE2 to mediate viral infection is not known. B0AT1 mutations cause Hartnup disorder, a condition characterized by neutral aminoaciduria and, in some cases, pellagra-like symptoms, such as photosensitive rash, diarrhea, and cerebellar ataxia. Correspondingly, the lack of ACE2 and the concurrent absence of B0AT1 expression in small intestine causes a decrease in l-tryptophan absorption, niacin deficiency, decreased intestinal antimicrobial peptide production, and increased susceptibility to inflammatory bowel disease (IBD) in mice. Thus, the abundant expression of ACE2 in small intestine and its association with amino acid transporters appears to play a crucial role for the digestion of peptides and the absorption of amino acids and, thereby, for the maintenance of structural and functional gut integrity.

S2044 A Rare Case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Hartnup Disease

INTRODUCTION: Niacin Deficiency is an uncommon finding in developed countries and is usually secondary to poor dietary intake. A rare cause is Hartnup Disease, which leads to malabsorption of amino acids, specifically tryptophan. Patients may present with Pellagra, a constellation of symptoms that include dermatitis, diarrhea, and neurological abnormalities. We present a case of a patient infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) who presented with Pellagra and Niacin deficiency secondary to undiagnosed Hartnup disease. CASE DESCRIPTION/METHODS: A 46-year-old male without significant medical history presented with complaints of fever, polydipsia, polyuria, non-bloody diarrhea and dyspnea. Labs revealed a positive SARS-CoV-2 test. During his hospital course, the patient developed confusion, disorientation and required supplemental oxygen. His polydipsia and polyuria worsened and his diarrhea was persistent. His physical exam revealed a pigmented rash that was diffuse on bilateral lower and upper extremities. Niacin deficiency was suspected to be the etiology of his symptoms. A urine chromatography was obtained (Figure 1), which was consistent with Hartnup disease. Niacin supplementation was administered with subsequent resolution of the patient’s symptoms. He was discharged home with instructions to continue to take multivitamins. DISCUSSION: Our case describes a patient infected with SARS-CoV-2, which may have led to amino acid deficiencies inducing pellagra in a previously asymptomatic patient with Hartnup disease. It has previously been reported that Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) downregulates ACE2 expression in the GI tract. This leads to impaired amino acid absorption, specifically tryptophan. We hypothesize that similar to its previous generation, the novel SAR-CoV-2 may also downregulate ACE2 expression in the GI tract leading to malabsorption and a deficiency of amino acids. We suggest that it was by this mechanism that the patient’s infection precipitated symptoms of niacin deficiency in the setting of underlying Hartnup disease. This case serves to raise awareness that SARS-CoV-2 may be altering reabsorption of nutrients in the GI tract and leading to the development of new nutritional deficiencies or exacerbating previously undiagnosed inborn errors of intestinal nutrient absorption.Figure 1.: Urine Chromatography.Figure 2.: Urine Chromatography.

The Nutrition-Focused Physical Examination: Added Value for Patients and Clinicians

The Nutrition-Focused Physical Examination: Added Value for Patients and Clinicians

Development of an adverse drug event network to predict drug toxicity

Despite of their therapeutic effects, drug's exposure may have negative effects on human health such as adverse drug reaction (ADR) and side effects (SE).Adverse drug events (ADEs), that correspond to an event occurring during the drug treatment (i.e. ADR and SE), is not necessarily caused by the drug itself, as this is the case with medical errors and social factors. Due to the complexity of the biological systems, not all ADEs are known for marketed drugs. Therefore, new and effective methods are needed to determine potential risks, including the development of computational strategies. We present an ADE association network based on 90,827 drug-ADE associations between 930 unique drug and 6221 unique ADE, on which we implemented a scoring system based on a pull-down approach for prediction of drug-ADE combination. Based on our network, ADEs proposed for three drugs, safinamide, sonidegib, rufinamide are further discussed. The model was able to identify, already known drug-ADE associations that are supported by the literature and FDA reports, and also to predict uncharacterized associations such as dopamine dysregulation syndrome, or nicotinic acid deficiency for the drugs safinamide and sonidegib respectively, illustrating the power of such integrative toxicological approach.

MON-911 Debilitating Neuropsychiatry Symptoms in Pancreatic Insulinoma Co-Secreting Serotonin and IGF-1

Background:Insulinoma is the most common type of functioning pancreatic neuroendocrine tumor (NET). Polyhormonal secretions from the NET, giving rise to distinct clinical symptoms such as carcinoid symptoms are rare. Clinical Case: We report a 68-year-old woman who presented with four months history of recurrent diaphoresis, palpitations, tremors and chest tightness. These were associated with episodic paroxysms of flushing and diarrhoea. The physical examination was unremarkable. She was a well-nourished woman with BMI of 28 kg/m2. Initial laboratory tests ruled out any renal, liver abnormalities with normal cortisol and thyroid function test. Further evaluation confirms insulin mediated hypoglycaemia with low random blood sugar 2.5 mmol/l (4.4-7.8) and failure to suppress C-peptide, 1092 pmol/L (298-2350) and insulin levels, 12.7 mU/L (3-25). Urine 5-HIAA was markedly elevated 2430.37 µmol/day (3.66-42.89) with borderline elevation of serum chromogranin A level 122 ng/mL (27-94). IGF-1 was also raised at 416 ug/L (91-282). Two months later she presented with new onset of delirium, incoherence, agitation and restlessness independent of her hypoglycaemic events. These symptoms deteriorated and fluctuates throughout the day with period of normalcy in between. This has led to requirement of a full time caregiver for her. Cranial CT excluded any brain pathology. We are faced with a diagnostic challenge to localize the primary lesion as radiological imaging so far were normal. GALLIUM-68 PET CT showed physiological uptake in the uncinate process of the pancreas (SUVmax 14.4). Endoscopic ultrasound of the pancreas was normal. An intra-arterial calcium stimulation test with hepatic venous sampling (ASVS) confirms a lesion at the head of pancreas with two times increment of insulin from baseline at the gastroduodenal artery distribution. Despite elimination of hypoglycaemic events with Diazoxide 100mg twice daily, her neuropsychiatric symptoms persisted. We postulate that this might be from excessive peripheral production of serotonin by the pancreatic carcinoid tumour or a niacin deficiency state because of metabolic diversion of its precursor, tryptophan. Conclusion:This case highlights the occurrence of debilitating neuropsychiatry manifestations in a likely neuroendocrine tumour arising from the head of pancreas secreting insulin, serotonin and IGF-1.

Pemphigus Pellagrosus masquerading as cutaneous adverse drug reaction

Pellagra is caused by cellular deficiency of niacin or its precursor amino acid, tryptophan. Niacin, also known as nicotinic acid or vitamin B3 is essential for carbohydrate, fat, protein and alcohol metabolism, detoxification of drugs and reactive oxygen species, cell signaling and DNA repair.. Classically characterized by a symmetric photodistributed skin rash, gastrointestinal symptoms, and neurologic and psychiatric disturbances (dermatitis, diarrhea, and dementia), it can lead to death if left untreated. The dermatitis caused by pellagra can present in the acute phase with vesicles and bullae, resembling a sunburn in its early stages (wet pellagra).When pellagra recurs at the same site, blisters may occur (pemphigus pellagrosus). Histopathologic changes in the acute phase can include intra- or subepidermal vesicle formation as a result of spongiosis, ballooning degeneration, and vacuolar alteration of the basal layer. The preferred therapy is with nicotinamide because it does not cause the flushing observed with niacin. Initially Patient was started on injection nicotinamide (200mg) twice daily .Later patient was shifted to oral nicotinamide 50 mg twice daily resulted in significant improvement in tenderness, burning discomfort, and desquamation . It is, therefore, important for dermatologists to be aware of the growing body of literature pertaining to nutrition and skin disease to appropriately inform patients on benefits and harms of specific dietary interventions.

肠梗阻并发烟酸缺乏症1例

肠梗阻并发烟酸缺乏症1例

THE CONSUMPTION OF VITAMINS BY THE POPULATION OF WORKING AGE (ON THE EXAMPLE OF REPUBLIC OF TATARSTAN)

To assess the level of consumption of vitamins entering the body with food, vitamin and mineral complexes, and enriched food in the population of working age of the Republic of Tatarstan. The quantitative content of vitamin A and ß-carotene in the diet of men and women is 2 or more times lower than normal value. Indices of the daily intake of vitamin C are 3 times less than normal. Significant differences in the intake of vitamins with food depending on the group of physical activity were not revealed (p > 0.05). Combined deficiency of retinol, β-carotene, thiamine, Riboflavin, Niacin, and ascorbic acid can be traced in 86% of diets. 13.2% of women and 3.7% of men use vitamin and mineral complexes every day; 48% of respondents fail to use them, the rest (35.1%) persons use irregularly. The intake of vitamin and mineral complexes correlates with the average monthly income and the level of education of the respondents (p ≤ 0.05). 3% of respondents consume enriched food 1-2 times a week. The majority of respondents (73%) do not know about products with high nutritional value, the rest (24%), use enriched products 1-2 times a month. We have not found a relationship between the number of enriched products consumed, family income and education level (p > 0.05).