Pellagra Research Articles

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.

Abstract 3022: GPR109A activation limits cell growth by inducing p53 and its targets in human colon cancer cells

Abstract Chemical carcinogens or xenobiotics present in the diet play a significant role in colon cancer (CC) formation. p53, a tumor suppressor and multi-functional protein, provides an important barrier against the initiation and maintenance of CC. p53 mutation or inactivation is observed in about 60% of CCs and about 90% of all cancers. Therefore, therapeutic avenues that will rejuvenate wild-type p53 or target mutant p53 should have a significant impact on the prevention and treatment of CC. GPR109A, a G-protein coupled receptor for the FDA-approved lipid-lowering drug Niacin (NA), bacterial metabolite Butyrate (BTR), and ketone body β-hydroxybutyrate (BHB), functions as a novel tumor suppressor in the colon by providing the molecular link between colonic bacteria and p53 function. GPR109A activation limits cAMP by inhibiting adenylate cyclase (AC), which induces RAS and its downstream growth-promoting signaling. cAMP also enhances the binding of MDM2 to p53 and induces the proteasomal degradation of p53. p53 is an NAD+-dependent molecule and deficiency of NA, the precursor of NAD+, impairs p53 function. We tested the role of GPR109A and its agonists (NA, BTR, and BHB) in normal immortalized colon epithelial cell lines (CCD33 and CCD81) and various CC lines such as HCT116-p53+/+, HCT116-p53−/−, DLD1 (p53 point mutation), VACO4A (p53 insertion mutation), and SW498 (p53 deletion) and measured cell proliferation, cell cycle, apoptosis, and analyzed the expression of GPR109A and p53 (total, phosphorylated, and acetylated), MDM2, p21, Bax, and Puma in the presence and absence of GPR109109 agonists. We found that GPR109A expression is significantly reduced in CC cell lines, especially in p53 mutant cell lines, when compared to normal immortalized colonic epithelial cell lines. Treatment of CC cell lines with GPR109A agonists-induced apoptosis in wild-type p53 expressing CC by activating p53 and its targets. However, some lesser extent in p53 mutant or p53 null cell lines. Lentiviral-mediated GPR109A expression in CC cell lines itself induced apoptosis in both wild-type and mutant p53 expressing CC cell lines and GPR109A agonists treatment induced further. Interestingly, GPR109A agonists BTR and BHB significantly increased apoptosis in p53 mutant and p53 null CC cell lines in a p53-independent manner. Overall, our results provide evidence that GPR109A activation can be used as an effective therapeutic strategy for the treatment of CC. Citation Format: Muthusamy Thangaraju, Nanditi N. Thangaraju, Lauren Gilstrap, Madison Chimenti, Tulshi Patel, Sathish Sivaprakasam, Nikhil Patel, Santhakumar Manicassamy, Puttur D. Prasad, Vadivel Ganapathy. GPR109A activation limits cell growth by inducing p53 and its targets in human colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3022.

Chronic Ethanol Intake Impairs Niacin Nutritional Status in Mice.

Niacin is involved in many biological reactions relating energy metabolism, redox reactions, DNA repair and longevity. Since niacin deficiency has been reported in alcoholic patients, and niacin coenzyme NAD is used as substrate to dehydrogenate ethanol in the liver, ethanol consumption can be a factor to impair 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 ethanol intake on niacin nutritional status, 4 wk old KMO-/- mice were fed 4 or 30 mg/kg nicotinic acid containing diets with or without 15% ethanol for 35 d. The mice fed 4 mg/kg nicotinic acid diet with ethanol showed lower body weight gain and niacin nutritional markers such as liver and blood NAD, and urine nicotinamide metabolites than the mice without ethanol. These animals did not show any difference in the NAD synthesis, NAD salvage and nicotinamide catabolic pathways. Chronic ethanol intake 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 ethanol-induced growth retardation, their body weight rapidly increased. These results show that chronic ethanol intake impairs niacin nutritional status in the niacin insufficient mice, and enough niacin intake can prevent this impairment. Our findings also suggest that chronic ethanol intake increases niacin requirement by increase of NAD consumption.

The Guard, His Gauntlet and Goblet- An Atypical Presentation of Pellagra in a Chronic Alcoholic

Alcoholism a chronic condition affects multiple organ systems including skin. Dermatological markers of alcohol abuse are invaluable. Despite this, association of skin diseases and alcohol misuse maybe overlooked or physicians fail to explore. Pellagra is a multifactorial disease caused by Niacin/Tryptophan deficiency. It exhibits photodermatitis, gastrointestinal and neuropsychiatric manifestations. Chronic alcoholics are at risk. Considering pellagra as differential diagnosis in chronic alcoholics with these symptoms is crucial. This disease is easily treatable but if missed proves fatal. Hence, its recognition is important in other clinical settings for comprehensive treatment. The pathognomonic presentation of Pellagra is the Casal necklace, but here we present a case of 34year old alcoholic with an atypical presentation of Pellagra. Chronic alcoholics need evaluation for Pellagra amongst other nutritional deficiencies which due to diverse presentation can be missed. Early diagnosis and treatment can avoid impending neuropsychiatric complications. Due to participation of numerous disciplines consultation liaison psychiatry is vital here. Keywords: Alcohol dependence, Alcohol cutaneous manifestations, Pellagra, Niacin deficiency, Alcohol biomarkers

Micronutrient gaps during the complementary feeding period in seven countries in Southeast Asia: A Comprehensive Nutrient Gap Assessment

AbstractThe complementary feeding period is a critical stage of child development when micronutrient needs are high and challenging to meet. Understanding if specific micronutrient gaps exist during this period is critical for effective programming. A Comprehensive Nutrient Gap Assessment (CONGA) was conducted in seven countries in Southeast Asia to estimate gaps in micronutrients commonly lacking in the diets of children aged 6–23 months and to establish the certainty of available evidence for each identified gap. Sixty‐eight evidence sources were identified during this analysis, and 310 micronutrient‐specific data points were identified across all seven countries. Data points varied in recency, representativeness and evidence type. The CONGA methodology enabled the estimation of a gap burden rating for each micronutrient in each country, as well as a rating of their evidence certainty. Micronutrient gaps were identified in vitamin D, zinc and iron and a potential gap was identified in calcium during the complementary feeding period in the region. Evidence relevant to intake and deficiency of folate, vitamin B12, thiamine, niacin, vitamin C and vitamin B6 was limited across the region. Proven strategies to address these gaps include increasing the availability and consumption of nutrient‐dense foods, micronutrient supplementation, large‐scale fortification of staple foods and condiments and point‐of‐use fortification through multiple micronutrient powders and fortified speciality foods. More recent data on micronutrient availability, intake and deficiency is urgently needed in Southeast Asia.

Involvement of ACE2 in the intestinal transport of amino acids: Possible health and nutritional consequences in altered expression

Background:Absorption of neutral amino acids across the intestinal cells is mediated by the broad neutral amino acid transporter B0AT1. Intestinal expression of B0AT1 depends on the coexistence with the membrane-attached angiotensin-converting enzyme 2 (ACE2) which binds to the B0AT1 or the sodium-dependent imino-acid transporter 1 (SIT1) in the intestinal epithelial cells. Objectives:The objective of this article is to provide an overview of the involvement of ACE2 in the transport of amino acids from the intestinal lumen and possible harmful effects on health and nutrition due to altered ACE2 expression. Methods: PubMed, Scopus, and Google Scholar were searched using the keywords ACE2 paired with intestinal and gut B0AT1, SIT1, amino acid transport or absorption, health, and nutrition. Expression of B0AT1 in the intestine was completely absent in ACE2 knockout mice. Lack of ACE2 and B0AT1 expression lead to low plasma and muscle tryptophan, niacin deficiency, decreased intestinal antimicrobial peptide, and increased susceptibility to inflammatory bowel disease in animal models. Results: Expression of ACE2 in the small intestine and its association with amino acid transporters play a crucial role in the absorption of amino acids, maintenance of structural and functional gut integrity and overall health and nutrition status of an individual. Bangladesh Journal of Medical Science Vol. 22 No. 04 October’23 Page : 729-733

Pathophysiology and clinical management of pellagra - a review.

Pellagra is a rare disease caused by niacin deficiency or a disruption of its metabolism. Its manifestations are dermatitis with pronounced photosensitivity, gastrointestinal symptoms, and neuropsychiatric ailments. Currently pellagra is developed in people who chronically abuse alcohol or are treated with medications from specific pharmacological groups (immunosuppressive and anti-tuberculosis drugs). Although the root cause of the disease was established in the mid-twentieth century, a detailed explanation of the processes leading to the development of symptoms has not yet been proposed. They include complex abnormalities at the molecular, metabolic, and immunological levels. Diagnostics is based primarily on the clinical presentation of the disease, while auxiliary tests play secondary role. The low prevalence of the disease, meaning that physicians are unfamiliar with its recognition, often leads to delays in diagnosis and appropriate treatment. The therapy is causal and based on administering niacinamide. Failure to implement treatment in the early stages of the disease leads to the patient's death. The aim of this literature review is to summarize the current state of knowledge on the pathomechanisms of pellagra, highlighting the clinical implications, and key elements of diagnostic and therapeutic management that are important in the treatment of pellagra patients.

The effect of dietary niacin deficiency on reproduction of European brown hares: An experimental study

Large plots of maize in agricultural landscapes are associated with reduced reproductive output of females and impaired population development of free-living populations of European brown hares ( Lepus europaeus , Pallas 1778). We investigated in captive brown hares experimentally whether these effects could result from an undersupply of niacin due to a suspected maize-biased diet in such areas. We repeatedly mated adult female hares, fed ad libitum either with a niacin deficient pellet mainly consisting of maize plant parts, or with the same pellet enriched with niacin to meet physiological requirements. We measured effects of the experimental feeding on body mass of females, reproductive output, growth and survival of leverets. We found significantly higher body mass of females fed the control pellet, and faster body mass gain of their leverets until standardized weaning. We found no significant difference between niacin deficient and control diet groups in reproductive output of females and survival rates of leverets. Our results show that even a diet severely depauperate of niacin affects reproductive success of female brown hares only slightly, presumably because of sufficient conversion of tryptophan to niacin, or of additional supply of niacin by caecal microorganism.

Poly(ADP-Ribose) Polymerase Activity and DNA Strand Breaks Are Affected in Tissues of Niacin-Deficient Rats

The niacin cofactor, NAD, is the substrate for poly(ADP-ribose) polymerase, an enzyme associated with DNA repair. We investigated, therefore, whether hepatic poly(ADP-ribose) polymerase activity was altered and DNA strand breaks in lymphocytes and liver were greater in niacin-deficient rats. A niacin deficiency was established in weanling rats with diets containing 1.5 mg/kg of niacin. Based on lower growth rates and NAD concentrations in blood, liver and skeletal muscle, this diet maintained rats in a deficient state for 1 mo, and, when the dietary niacin was reduced to 0.5 mg/kg, rats remained deficient for an additional month. The hepatic poly(ADP-ribose) polymerase activity was decreased in one experiment when mean hepatic NAD concentrations were 0.60 and 0.51 mumol/g at d 34 and d 60, respectively, compared with 0.77 and 0.80 mumol/g in pair-fed controls. Enzyme activity, however, was greater than in controls when hepatic NAD concentrations were < 0.30 mumol/g. Strand breaks in DNA did not accumulate except after tissues were exposed to hypoxanthine-xanthine oxidase, a free radical-generating system. Exposure to this system caused more DNA strand breaks in lymphocytes and hepatic nuclei from niacin-deficient rats compared with the same tissues from controls. The results suggest that, in rats, although hepatic poly(ADP-ribose) polymerase activity can be elevated, a severe niacin deficiency may increase the susceptibility of DNA to oxidative damage, likely due to a lower availability of NAD.

Corrigendum: Maize monoculture causes niacin deficiency in free-living European brown hares and impairs local population development

Corrigendum: Maize monoculture causes niacin deficiency in free-living European brown hares and impairs local population development

Carbamazepine-induced pellagra: Dermoscopic findings and response to oral nicotinamide

ABSTRACT Pellagra is a nutritional disorder characterized clinically by the four Ds: dermatitis, diarrhea, dementia, and severe systemic photosensitivity manifesting as death. The disorder results from a deficiency of niacin or its precursor tryptophan and is mainly associated with compromised dietary intake of niacin and tryptophan or excessive intake of leucine (a natural antagonist). Other causes include chronic alcohol intake, malabsorption, metabolic disorders, and the administration of certain medications. Herein, we report the clinical and dermoscopic findings in a twenty-year-old male with seizure disorder presenting with carbamazepine-induced pellagrous dermatitis that resolved after the administration of niacin. Key words: Pellagra; Photosensitivity; Carbamazepine; Dermoscopy; Niacin

Pellagra and alcoholism: case report

Pellagra is mainly caused by a niacin deficiency or its precursor amino acid, tryptophan. We report a case of a male patient, 34 years old, a chronic alcoholic with delirium tremens and gastrointestinal symptoms (diarrhea, inappetence, and heartburn). He presented erythematous-brown, scaly, and well-defined plaques dispersed throughout the integument (photo-exposed areas) for 2 months that evolved with ulceration and hematic crusts. The case was diagnosed as pellagra associated with secondary bacterial infection and treated with rest, an unrestricted diet, B-complex replacement, abstention from alcohol, restriction of sun exposure, and broad-spectrum antibiotic therapy. The treatment allowed for significant improvement of symptoms in one week. Aspects of the pathophysiology and differential diagnoses of this condition are discussed, reinforcing the importance of considering pellagra in diagnosing patients with skin lesions associated with risk factors for malnutrition.

Impacts of Dietary Protein and Niacin Deficiency on Reproduction Performance, Body Growth, and Gut Microbiota of Female Hamsters (Tscherskia triton) and Their Offspring.

Food resources are vital for animals to survive, and gut microbiota play an essential role in transferring nutritional materials into functional metabolites for hosts. Although the fact that diet affects host microbiota is well known, its impacts on offspring remain unclear. In this study, we assessed the effects of low-protein and niacin-deficient diets on reproduction performance, body growth, and gut microbiota of greater long-tailed hamsters (Tscherskia triton) under laboratory conditions. We found that maternal low-protein diet (not niacin deficiency) had a significant negative effect on reproduction performance of female hamsters (longer mating latency with males and smaller litter size) and body growth (lower body weight) of both female hamsters and their offspring. Both protein- and niacin-deficient diets showed significant maternal effects on the microbial community in the offspring. A maternal low-protein diet (not niacin deficiency) significantly reduced the abundance of major bacterial taxa producing short-chain fatty acids, increased the abundance of probiotic taxa, and altered microbial function in the offspring. The negative effects of maternal nutritional deficiency on gut microbiota are more pronounced in the protein group than the niacin group and in offspring more than in female hamsters. Our results suggest that a low-protein diet could alter gut microbiota in animals, which may result in negative impacts on their fitness. It is necessary to conduct further analysis to reveal the roles of nutrition, as well as its interaction with gut microbes, in affecting fitness of greater long-tailed hamsters under field conditions. IMPORTANCE Gut microbes are known to be essential for hosts to digest food and absorb nutrients. Currently, it is still unclear how maternal nutrient deficiency affects the fitness of animals by its effect on gut microbes. Here, we evaluated the effects of protein- and niacin-deficient diets on mating behavior, reproduction, body growth, and gut microbiota of both mothers and offspring of the greater long-tailed hamster (Tscherskia triton) under laboratory conditions. We found that a low-protein diet significantly reduced maternal reproduction performance and body growth of both mothers and their offspring. Both protein and niacin deficiencies showed significant maternal effects on the microbial community of the offspring. Our results hint that nutritional deficiency may be a potential factor in causing the observed sustained population decline of the greater long-tailed hamsters due to intensified monoculture in the North China Plain, and this needs further field investigation.

Maize monoculture causes niacin deficiency in free-living European brown hares and impairs local population development

Maize (Zea mays) is the most produced crop worldwide and the second most important bio-energy plant. Huge maize monoculture is considered a threat to biodiversity in agricultural landscapes and may also contribute to the decline of European brown hares (Lepus europaeus, Pallas 1778). Indeed, the intensification of agriculture has been identified as one of the main factors responsible for the decline of brown hare populations. A reason why large maize cultures can be particularly detrimental to animals consuming this plant is its poor nutritional value with respect to niacin. In this study, we investigated the effects of the proportion of area under maize crops on liver concentrations of niacin in free-living hares, on the reproductive output of does (females), and on the development of local populations, at nine study sites in Lower Austria. Hare numbers were estimated from spotlight counts in spring and autumn. Liver samples and uteri were obtained from hares shot in the same areas during regular autumn hunts. Number of offspring born to an individual female during the preceding reproductive period was determined by counting placental scars. Our results show a significant negative effect of the area under maize crops on liver concentrations of niacin of does and on their reproductive output. Further, we found a significant negative effect of the area under maize on the development of a population. Altogether, our findings indicate that high proportions of the area under maize crops contribute to the decline of brown hares by reduced fecundity of does and impaired development of local populations.

NAD+ precursor concentrations are elevated in the follicular fluid of mares following oral supplementation of nicotinic acid

Niacin deficiency has recently been associated with congenital malformations in humans and embryonic death and resorption in mice (Shi et al. New England Journal of Medicine. 2017; 377(6):544-552). Mares suffer from high rates of early embryonic loss (Newcombe. Equine Veterinary Education. 12(2):88-101), the aetiology of which remains unknown. Increasing the levels of nicotinamide adenine dinucleotide (NAD+) through supplementing NAD+ precursors has resulted in an improvement in oocyte quality in mice (Bertoldo et al. Cell Rep. 2020; 30: 1670-1681). However, little is known regarding the requirement of niacin and NAD+ in reproductive processes in the mare. The aim of this study was to determine the effect of oral nicotinic acid (NA) supplements, a form of niacin, on the composition of nicotinamide adenine dinucleotide (NAD+) metabolites in the blood and follicular fluid of mares. Vehicle alone or NA (3 g per os) was administered to 7 mares over a minimum of 3 consecutive days during the oestrous cycle. Blood samples were collected immediately prior tosupplemental feeding and at follicular fluid aspiration. Follicular fluid was collected from the dominant follicle through transvaginal ultrasound guided aspiration. Blood and follicular fluid samples were processed and analysed by mass spectrometry. The concentration of nicotinamide mononucleotide (NMN) in the follicular fluid of NA-fed mares was greater than that in the corresponding plasma (15.0 ± 6.5 vs. 3.3 ± 0.9 ng/µL; p < 0.05) and in the follicular fluid of vehicle-fed mares (1.5 ± 0.5 ng/µL; p < 0.001). Meanwhile, the concentration of NA, nicotinamide (NAM) and nicotinuric acid (NUR) tended to be greater in the follicular fluid of NA supplemented mares (1043.9 ± 953.5, 1641.7 ± 256.1 and 5.5 ± 5.1 ng/µL) than in the corresponding plasma (70.8 ± 15.4, 875.6 ± 361.1 and 0.6 ± 0.2, respectively; p < 0.1). The results show that NA supplementation increased the bioavailability of NAD+ precursors in the follicular fluid of the dominant follicle, which is proposed to better promote the maturation of good quality oocytes, especially in older mares.

Clinical analysis of alcoholic pellagra: A single‐center retrospective study

Pellagra caused by niacin deficiency in alcoholics can be easily misdiagnosed because of similar symptoms to other alcohol-related diseases and the lack of the classical triad of signs. This study aimed to define the clinical presentation of alcoholic pellagra for early diagnosis and timely treatment. The clinical data of 16 alcohol-dependent patients who had pellagra and treated in our hospital from January 2002 to December 2019 were retrospectively analyzed. The local medical ethics committee approval (Medical Ethics Committee of Affiliated Hospital of XuZhou Medical University, XYFY2020-KL247-02) for this study has been obtained. The main complaints of the 16 patients were skin lesions (six cases), diarrhea (six cases), and mental disorders (four cases). Then, 13 cases had typical skin lesions, and 3 patients had a full spectrum of diarrhea, dementia, and dermatitis (3D). In terms of the main diagnosis, 2 patients had pellagra and Wernicke's encephalopathy, 3 patients had pellagra and alcohol-withdrawal syndrome, and the other patients had pellagra. After sufficient amounts of niacin and multivitamin B were given, clinical symptoms improved rapidly, and no sequelae were observed during follow-up. Pellagra is rarely manifested as a full 3D spectrum, with only one or two characteristics, which lack diagnostic specificity, especially in individuals with alcoholism. Physicians should maintain a high degree of suspicion of niacin deficiency in alcoholics. Alcohol-dependent patients with pellagra may be accompanied by complications of Wernicke's encephalopathy and alcohol-withdrawal syndrome. Prompt identification and timely treatment with a sufficient amount of niacin in combination with other vitamins and a certain amount of Zn can achieve a good prognosis of pellagra.

Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study

Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173.

Niacin Limitation Promotes Candida glabrata Adhesion to Abiotic Surfaces.

Candida glabrata is a prevalent fungal pathogen in humans, which is able to adhere to host cells and abiotic surfaces. Nicotinic acid (NA) limitation has been shown to promote the adherence of C. glabrata to human epithelial cells. Clinically, the elderly and hospitalized patients who are prone to C. glabrata–related denture stomatitis often suffer from vitamin deficiency. This study aimed to investigate C. glabrata adhesion to abiotic surfaces, including acrylic resin (a denture material) surfaces, cell surface hydrophobicity and adhesion gene expression. C. glabrata CBS138 was grown in media containing decreasing NA concentrations (40, 0.4, 0.04 and 0.004 µM). Adherence of C. glabrata to glass coverslips and acrylic resin was analyzed. C. glabrata adhesion to both surfaces generally increased with decreasing NA concentrations. The highest adhesion was found for the cells grown with 0.004 µM NA. The cell surface hydrophobicity test indicated that NA limitation enhanced hydrophobicity of C. glabrata cells. Quantitative PCR showed that of all adhesion genes tested, EPA1, EPA3 and EPA7 were significantly up-regulated in both 0.004 µM NA and 0.04 µM NA groups compared to those in the 40 µM NA group. No significant up- or down-regulation under NA limitation was observed for the other tested adhesion genes, namely AWP3, AWP4, AWP6 and EPA6. NA limitation resulted in increased expression of some adhesion genes, higher surface hydrophobicity of C. glabrata and enhanced adhesion to abiotic surfaces. NA deficiency is likely a risk factor for C. glabrata–related denture stomatitis in the elderly.

Effect of maternal dietary niacin intake on congenital anomalies: a systematic review and meta-analysis.

The significance of niacin in embryonic development has clinical implications in the counseling of pregnant women and may be used to inform nutrition recommendations. This study, therefore, aims to review the associations between maternal periconceptional niacin intake and congenital anomalies. A systematic search of Ovid MEDLINE, ClinicalTrials.gov, AMED, CENTRAL, Emcare, EMBASE, Maternity & Infant Care and Google Scholar was conducted between inception and 30 September 2020. Medical subject heading terms included "nicotinic acids" and related metabolites, "congenital anomalies" and specific types of congenital anomalies. Included studies reported the association between maternal niacin intake and congenital anomalies in their offspring and reported the measure of association. Studies involved solely the women with co-morbidities, animal, in vitro and qualitative studies were excluded. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale (NOS). A random effects-restricted maximum likelihood model was used to obtain summary estimates, and multivariable meta-regression model was used to adjust study-level covariates. Of 21,908 retrieved citations, 14 case-control studies including 35,743 women met the inclusion criteria. Ten studies were conducted in the U.S, three in Netherlands and one in South Africa. The meta-analysis showed that expectant mothers with an insufficient niacin intake were significantly more likely to have babies with congenital abnormalities (odds ratio 1.13, 95% confidence interval 1.02-1.24) compared to mothers with adequate niacin intake. A similar association between niacin deficiency and congenital anomalies was observed (OR 1.15, 95% CI 1.03-1.26) when sensitivity analysis was conducted by quality of the included studies. Meta-regression showed neither statistically significant impact of study size (p = 0.859) nor time of niacin assessment (p = 0.127). The overall quality of evidence used is high-thirteen studies achieved a rating of six or seven stars out of a possible nine based on the NOS. Inadequate maternal niacin intake is associated with an increased risk of congenital anomalies in the offspring. These findings may have implications in dietary counseling and use of niacin supplementation during pregnancy.