Chronic Endurance Exercise Impairs Niacin Nutritional Status in Mice.

Niacin is a cofactor in many biological reactions related to energy metabolism, redox reactions, DNA repair and longevity. Although it has been considered that increasing energy expenditure increases NAD consumption, little study has directly demonstrated the effect of exercise on niacin nutritional status. We have recently established the niacin insufficient model mice using kynurenine 3-monooxygenase knock out (KMO-/-) mice with niacin-limited diet, which lack the de novo NAD synthesis pathway from tryptophan. To evaluate the effects of chronic endurance exercise on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets, and forced to swim in a running water pool every other day for 35 d. The swim-exercised mice fed 4 mg/kg nicotinic acid diet showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the sedentary mice. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic endurance exercise failed to affect any indices in the mice fed the 30 mg/kg nicotinic acid diet. When the diet was exchanged the 4 mg/kg for 30 mg/kg nicotinic acid diet to the mice showed chronic endurance exercise-induced growth retardation, their body weight rapidly increased. These results show that chronic endurance exercise impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic endurance exercise increases niacin requirement by increase of NAD consumption.

Fat and proteolysis due to methionine, tryptophan, and niacin deficiency leads to alterations in gut microbiota and immune modulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is one of the intractable diseases. Nutritional components associated with IBD have been identified, and it is known that excessive methionine intake exacerbates inflammation, and that tryptophan metabolism is involved in inflammation. Analysis of the gut microbiota has also progressed, where Lactobacillus regulate immune cells in the intestine and suppress inflammation. However, whether the methionine and tryptophan metabolic pathways affect the growth of intestinal Lactobacillus is unknown. Here we show how transient methionine, tryptophan, and niacin deficiency affects the host and gut microbiota in mouse models of colitis (induced by dextran sodium sulfate) fed a methionine-deficient diet (1K), tryptophan and niacin-deficient diet (2K), or methionine, tryptophan, and niacin-deficient diet (3K). These diets induced body weight decrease and 16S rRNA analysis of mouse feces revealed the alterations in the gut microbiota, leading to a dramatic increase in the proportion of Lactobacillus in mice. Intestinal RNA sequencing data confirmed that the expression of several serine proteases and fat-metabolizing enzymes were elevated in mice fed with methionine, tryptophan, and niacin (MTN) deficient diet. In addition, one-carbon metabolism and peroxisome proliferator-activated receptor (PPAR) pathway activation were also induced with MTN deficiency. Furthermore, changes in the expression of various immune-related cytokines were observed. These results indicate that methionine, tryptophan, and niacin metabolisms are important for the composition of intestinal bacteria and host immunity. Taken together, MTN deficiencies may serve as a Great Reset of gut microbiota and host gene expression to return to good health.

Declined flesh quality resulting from niacin deficiency is associated with elevated glycolysis and impaired mitochondrial homeostasis in grass carp (Ctenopharyngodon idella).

Energy metabolism exerts profound impacts on flesh quality. Niacin can be transformed into nicotinamide adenine dinucleotide (NAD), which is indispensable to energy metabolism. To investigate whether niacin deficiency could affect energy metabolism and flesh quality, six diets with graded levels of 0.49, 9.30, 21.30, 33.30, 45.30 and 57.30 mg/kg niacin were fed to grass carp (Ctenopharyngodon idella) for 63 days. The results showed that niacin deficiency declined flesh quality by changing amino acid and fatty acid profiles, decreasing shear force, increasing cooking loss and accelerating pH decline. The accelerated pH decline might be associated with enhanced glycolysis as evident by increased hexokinase (HK), pyruvate kinase (PK) and lactic dehydrogenase (LDH) activities, and mitochondrial dysfunction as evident by destroyed mitochondrial morphology, impaired respiratory chain complex I and antioxidant ability. Based on PWG and cooking loss, the niacin requirements for sub-adult grass carp were 31.95 mg/kg and 29.66 mg/kg diet, respectively.

A peculiarly characterised case of isoniazid-induced pellagra- 2 Ds and a C: a case report.

Niacin or tryptophan deficiency causes pellagra. Isoniazid interferes with the absorption of niacin and individuals on Isoniazid (INH) are at risk of pellagra. Isoniazid preventive therapy (IPT) is the administration of isoniazid to immunosuppressed individuals to prevent active tuberculosis (TB). IPT, in sub-Saharan Africa, the region worst hit by HIV and with a high TB prevalence, is recommended. A 40-year-old, HIV+ Zambian woman on Antiretroviral therapy for five years and IPT for three months presented with a four-day history of constipation, generalised body weakness and irrelevant talk. She complained of a generalised rash, sloughing off, and darkening of the skin on the face, neck, forearms, and dorsum of both feet. A physical examination revealed features of pellagra, and rapid response to oral niacin reaffirmed the diagnosis of pellagra. Unlike typical cases of pellagra presenting with the classic 3 Ds of Diarrhoea, Dementia and Dermatitis, our patient presented with constipation instead of diarrhoea. A consideration of Pellagra in HIV+ patients on IPT whose diet is mostly maize-based will be beneficial, even if the classic 3 Ds of diarrhoea, dementia, and dermatitis are not wholly present. A timely diagnosis and prompt treatment of pellagra can be lifesaving.

Pellagra, a re-emerging disease: a case report of a girl from a community ravaged by insurgency.

Pellagra is a nutritional disorder of niacin deficiency which is characterized by triad of dermatitis, diarrhea and dementia. It is often seen in a state of poor nutrition among alcoholics, homeless and patients suffering from malabsorption. Though seldom occurs in children, its re-emerging is seen as a result of worsening food security in vulnerable population during conflict or insurgency. We report the case of 12-year-old female pastoralist who presented darkening and thickening of the hands, feet, ankles, neck and her upper trunk. Conflicts and insurgency usually occur in resource constraint settings where health workers are few and overworked. Therefore, continuously educating health workers and the general public regarding nutrition and its disorders like pellagra is a priority. Public Health authorities and policy makers also ought to take pediatric nutrition serious in order to avoid its escalation in internally displaced persons or children orphaned by insurgency.

Pellagra in the USA: unusual manifestations of a rare entity.

The case involves a 62-year-old female native of the USA with a history of bipolar disorder and chronic obstructive pulmonary disease who presented with intractable diarrhoea. Prior to the index admission, she was admitted to the intensive care unit and required pericardiocentesis for an idiopathic pericardial effusion with tamponade physiology. Following discharge, she suffered intractable diarrhoea and represented for medical evaluation. She had a painful, swollen tongue as well as persistent hypoglycaemia and required glucose infusions. She had adrenal function testing which revealed adrenal insufficiency. Vitamin testing revealed normal B12 and folate levels but undetectable levels of thiamine, riboflavin and niacin. Her symptoms and signs resolved entirely with appropriate vitamin supplementation. Niacin (vitamin B3) is essential for multiple metabolic pathways, and severe deficiency may cause clinical syndrome of pellagra which is most commonly associated with diarrhoea, delirium and dermatitis. Additional physiological derangements may include adrenal insufficiency, insulin hypersensitivity and pericarditis.

[Skin Manifestations of Pellagra].

Pellagra is a type of dietary deficiency disease caused by an insufficiency of niacin or tryptophan. Symptoms of pellagra include diarrhea, dermatitis, and dementia. It is usually diagnosed based on a patient's dietary history and clinical symptoms. The diagnostic triad of pellagra includes symptoms of dermatitis, dementia, and diarrhea. Dermatitis is important for the diagnosis of this condition, because dementia and diarrhea show low specificity. In the modern era, pellagra rarely occurs in developed countries. However, pellagra should be considered in the differential diagnoses of dermatitis occurring on the sun-exposed areas of skin. Additionally, a hypoalimentation state with concomitant vitamin and/or zinc deficiency is observed in patients with pellagra. After checking the patient's overall nutritional status specifically with respect to pellagra, it is important to provide adequate food, supplemented with vitamins, zinc, and nicotinic acid to treat the patient's nutritional deficiencies.

Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications.

Niacin (also known as "vitamin B3" or "vitamin PP") includes two vitamers (nicotinic acid and nicotinamide) giving rise to the coenzymatic forms nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The two coenzymes are required for oxidative reactions crucial for energy production, but they are also substrates for enzymes involved in non-redox signaling pathways, thus regulating biological functions, including gene expression, cell cycle progression, DNA repair and cell death. In the central nervous system, vitamin B3 has long been recognized as a key mediator of neuronal development and survival. Here, we will overview available literature data on the neuroprotective role of niacin and its derivatives, especially focusing especially on its involvement in neurodegenerative diseases (Alzheimer's, Parkinson's, and Huntington's diseases), as well as in other neuropathological conditions (ischemic and traumatic injuries, headache and psychiatric disorders).

Niacin deficiency modulates genes involved in cancer: Are smokers at higher risk?

The role of niacin's metabolite, nicotinamide adenine dinucleotide (NAD), in DNA repair via base-excision repair pathway is well documented. We evaluated if niacin deficiency results in genetic instability in normal human fetal lung fibroblasts (MRC-5), and further, does it leads to enhanced accumulation of cigarette smoke-induced genetic damage? MRC-5 cells were grown discretely in niacin-proficient/deficient media, and exposed to nicotine-derived nitrosamine ketone (NNK, a cigarette smoke carcinogen). Niacin deficiency abated the NAD polymerization, augmented the spontaneous induction of micronuclei (MN) and chromosomal aberrations (CA) and raised the expression of 10 genes and suppressed 12 genes involved in different biological functions. NNK exposure resulted in genetic damage as measured by the induction of MN and CA in cells grown in niacin-proficient medium, but the damage became practically marked when niacin-deficient cells were exposed to NNK. NNK exposure raised the expression of 16 genes and suppressed the expression of 56 genes in cells grown in niacin-proficient medium. NNK exposure to niacin-deficient cells raised the expression of eight genes including genes crucial in promoting cancer such as FGFR3 and DUSP1 and suppressed the expression of 33 genes, including genes crucial in preventing the onset and progression of cancer like RASSF2, JUP, and IL24, in comparison with the cells grown in niacin-proficient medium. Overall, niacin deficiency interferes with the DNA damage repair process induced by chemical carcinogens like NNK, and niacin-deficient population are at the higher risk of genetic instability caused by cigarette smoke carcinogen NNK.

Recognising the return of nutritional deficiencies: a modern pellagra puzzle.

A 34-year-old previously well woman presented with a 4-week history of diffuse erythema and crusting of skin affecting all four limbs. Examination revealed erythematous skin plaques associated with ulceration and fissuring affecting sun-exposed areas of all four limbs primarily on the dorsal surfaces, and a body mass index of 17 kg/m2 She was admitted under the infectious diseases unit, and an autoimmune and infective screen was performed which returned unremarkable. Dietetic consultation led to the diagnosis of severe protein-energy malnutrition, consequent to a severely restricted, primarily vegan, diet. Analysis of the patient's reported diet with nutritional software revealed grossly suboptimal caloric intake with risk of inadequacy for most micronutrients, vitamins and minerals, including niacin. Oral thiamine, multivitamin, iron supplementation and vitamin B complex were started, and a single intramuscular vitamin B12 dose was administered. Marked improvement was seen after 6 weeks, with near-complete resolution of skin changes. These findings supported a diagnosis of pellagra.

Alcoholic Pellagra as a Cause of Altered Mental Status in the Emergency Department.

BACKGROUND: Pellagra, which is caused by a deficiency of niacin and tryptophan, the precursor of niacin, is a rare disease in developed countries where alcoholism is a major risk factor due to malnutrition and lack of B vitamins. Although pellagra involves treatable dementia and psychosis, it is often underdiagnosed, especially in developed countries. CASE REPORT: In Japan, a 37-year-old man presented to the emergency department with altered mental status and seizures. Wernicke encephalopathy and alcohol withdrawal were suspected. The patient was treated with multivitamins, which did not include nicotinic acid amide, and oral diazepam. Despite medical treatment, his cognitive impairment progressively worsened, and eventually, pellagra was suspected. His response to treatment with nicotinic acid amide was substantial, and he was discharged without any long-term sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often underdiagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.

Adaptation of New Colombian Food-based Complementary Feeding Recommendations Using Linear Programming.

OBJECTIVE: The aim of the study was to use linear programming (LP) analyses to adapt New Complementary Feeding Guidelines (NCFg) designed for infants aged 6 to 12 months living in poor socioeconomic circumstances in Bogota to ensure dietary adequacy for young children aged 12 to 23 months. DESIGN: A secondary data analysis was performed using dietary and anthropometric data collected from 12-month-old infants (n = 72) participating in a randomized controlled trial. LP analyses were performed to identify nutrients whose requirements were difficult to achieve using local foods as consumed; and to test and compare the NCFg and alternative food-based recommendations (FBRs) on the basis of dietary adequacy, for 11 micronutrients, at the population level. RESULTS: Thiamine recommended nutrient intakes for these young children could not be achieved given local foods as consumed. NCFg focusing only on meat, fruits, vegetables, and breast milk ensured dietary adequacy at the population level for only 4 micronutrients, increasing to 8 of 11 modelled micronutrients when the FBRs promoted legumes, dairy, vitamin A-rich vegetables, and chicken giblets. None of the FBRs tested ensured population-level dietary adequacy for thiamine, niacin, and iron unless a fortified infant food was recommended. CONCLUSIONS: The present study demonstrated the value of using LP to adapt NCFg for a different age group than the one for which they were designed. Our analyses suggest that to ensure dietary adequacy for 12- to 23-month olds these adaptations should include legumes, dairy products, vitamin A-rich vegetables, organ meat, and a fortified food.

An Outbreak of Pellagra in the Kasese Catchment Area, Dowa, Malawi.

AbstractPellagra 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.

Neurodegeneration in equine grass sickness is not attributable to niacin deficiency.

BACKGROUND: The aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration in EGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi. OBJECTIVES: To compare the niacin status of EGS and control grazing horses. A secondary objective was to compare blood concentrations of vitamins B1, B2 and B6 in EGS and control grazing horses to determine if the status of these vitamins was altered in EGS. STUDY DESIGN: Case-control study. METHODS: Indices of niacin status, namely the erythrocyte nicotinamide adenine dinucleotide:nicotinamide adenine dinucleotide phosphate ratio (NAD:NADP ratio) and erythrocyte concentrations of NAD and NADP, were compared in blood collected from EGS and healthy control grazing horses. Blood concentrations of vitamins B1, B2 and B6 were also compared. RESULTS: There was no significant intergroup difference in the NAD:NADP ratio, the main index of functional niacin status (control group: median 2.1, interquartile range [IQR] 1.8-2.6; EGS group: median 2.1, IQR 1.9-2.6). EGS horses had significantly higher (median value increased by 25%) concentrations of NADP. There were no intergroup differences in blood concentrations of vitamins B1, B2 and B6. MAIN LIMITATIONS: The interpretation of data was limited by the lack of previously defined equine reference ranges for many of the analytes. Sample size was low. CONCLUSIONS: Niacin deficiency does not contribute to EGS neurodegeneration.

Skin findings associated with nutritional deficiencies.

Certain vitamin and mineral deficiencies may be recognized by their cutaneous signs. This case-based article reviews deficiencies of zinc and vitamins A, B2, B3, B6, and C, discussing their consequences and skin findings.

Deficiency of dietary niacin impaired gill immunity and antioxidant capacity, and changes its tight junction proteins via regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

To investigate the effects of dietary niacin on gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression, young grass carp (Ctenopharyngodon idella) were fed six diets containing graded levels of niacin (3.95-55.01 mg/kg diet) for 8 weeks. The study indicated that niacin deficiency decreased lysozyme and acid phosphatase activities, and complement 3 content, and caused oxidative damage that might be partly due to the decreased copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in fish gills (P < 0.05). Moreover, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor ß1), tight junction proteins (Occludin, zonula occludens 1, Claudin-15 and -3), signaling molecules (inhibitor of κBα (IκBα), target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and NF-E2-related factor 2 (Nrf2)) and antioxidant enzymes were significantly decreased (P < 0.05) in niacin-deficient diet group. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1ß), signaling molecules (nuclear factor kappa B p65, IκB kinase α, IκB kinase ß, IκB kinase γ, Kelch-like-ECH-associated protein 1b, myosin light chain kinase and p38 mitogen-activated protein kinase (p38 MAPK) were significantly increased (P < 0.05) in fish gills fed niacin-deficient diet. Interestingly, the varying niacin levels of 3.95-55.01 mg/kg diet had no effect on the mRNA level of Kelch-like-ECH-associated protein 1a, Claudin-c and -12 in fish gills (P > 0.05). In conclusion, niacin deficiency decreased gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling molecules of fish.

Deficiency of dietary niacin impaired intestinal mucosal immune function via regulating intestinal NF-κB, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

This study investigated the effects of dietary niacin on intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (255.63 ± 0.41 g) were fed six diets containing graded levels of niacin (3.95, 14.92, 24.98, 35.03, 44.97 and 55.01 mg/kg diet) for 8 weeks. Results observed that niacin deficiency decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 (C3) content in the intestine (P < 0.05), down-regulated mRNA levels of liver expressed antimicrobial peptide 2 (LEAP-2), hepcidin, interleukin 10, transforming growth factor ß1 and inhibitor of κBα (IκBα) (P < 0.05), up-regulated tumor necrosis factor α, interleukin 1ß, interferon γ2, interleukin 8, nuclear factor kappa B P65 (NF-κB P65), IκB kinase α (IKKα), IκB kinase ß (IKKß) and IκB kinase γ (IKKγ) in all intestinal segments of young grass carp (P < 0.05). In addition, niacin deficiency increased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC) contents, decreased glutathione content, and copper/zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferases (GST) and glutathione reductase (GR) activities in the intestine of young grass carp (P < 0.05). Additionally, niacin deficiency decreased mRNA levels of CuZnSOD, MnSOD, GPx, CAT, GST, GR, Claudin b, Claudin 3, Claudin c, Occludin, ZO-1, Claudin 15 and NF-E2-related factor 2 (Nrf2) (P < 0.05), and increased Claudin 12, Kelch-like ECH-associating protein 1a (Keap1a), myosin light-chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) mRNA expression levels in the intestine of young grass carp (P < 0.05), while the mRNA level of Kelch-like ECH-associating protein 1b (Keap1b) did not change (P > 0.05). In conclusion, niacin deficiency decreased intestinal mucosal immune and intestinal physical function, as well as regulated mRNA levels of NF-κB P65, IκBα, IKKα, IKKß, IKKγ, Nrf2, Keap1a, p38 MAPK and MLCK in the intestine of young grass carp. Based on the broken-line model analysis of intestinal lysozyme activity, the requirement of niacin for young grass carp (255.63 ± 0.41 g) were estimated to be 39.80 mg/kg diet.