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International Journal of Molecular... Nov 2019Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine... (Review)
Review
Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.
Topics: Animals; Energy Metabolism; Genomic Instability; Humans; Immunosuppression Therapy; NAD; Niacinamide; Skin Aging; Skin Neoplasms; Ultraviolet Rays
PubMed: 31779194
DOI: 10.3390/ijms20235946 -
The Lancet. Global Health May 2022Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and...
BACKGROUND
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.
METHODS
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.
FINDINGS
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.
INTERPRETATION
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.
FUNDING
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.
Topics: Antitubercular Agents; Case-Control Studies; Exanthema; Female; HIV Infections; Humans; Isoniazid; Male; Niacin; Pellagra; Tuberculosis; Vitamin B Complex
PubMed: 35427527
DOI: 10.1016/S2214-109X(22)00096-1 -
Cells Feb 2023Research into the functions of nicotinamide adenine dinucleotide (NAD) has intensified in recent years due to the insight that abnormally low levels of NAD are involved... (Review)
Review
Research into the functions of nicotinamide adenine dinucleotide (NAD) has intensified in recent years due to the insight that abnormally low levels of NAD are involved in many human pathologies including metabolic disorders, neurodegeneration, reproductive dysfunction, cancer, and aging. Consequently, the development and validation of novel NAD-boosting strategies has been of central interest, along with the development of models that accurately represent the complexity of human NAD dynamics and deficiency levels. In this review, we discuss pioneering research and show how modern researchers have long since moved past believing that pellagra is the overt and most dramatic clinical presentation of NAD deficiency. The current research is centered on common human health conditions associated with moderate, but clinically relevant, NAD deficiency. In vitro and in vivo research models that have been developed specifically to study NAD deficiency are reviewed here, along with emerging strategies to increase the intracellular NAD concentrations.
Topics: Humans; NAD; Pellagra; Clinical Relevance; Neoplasms; Aging
PubMed: 36766842
DOI: 10.3390/cells12030500 -
Molecular Genetics and Metabolism Jun 2022The NAD(P)HX repair system is a metabolite damage repair mechanism responsible for restoration of NADH and NADPH after their inactivation by hydration. Deficiency in... (Review)
Review
The NAD(P)HX repair system is a metabolite damage repair mechanism responsible for restoration of NADH and NADPH after their inactivation by hydration. Deficiency in either of its two enzymes, NAD(P)HX dehydratase (NAXD) or NAD(P)HX epimerase (NAXE), causes a fatal neurometabolic disorder characterized by decompensations precipitated by inflammatory stress. Clinical findings include rapidly progressive muscle weakness, ataxia, ophthalmoplegia, and motor and cognitive regression, while neuroimaging abnormalities are subtle or nonspecific, making a clinical diagnosis challenging. During stress, nonenzymatic conversion of NAD(P)H to NAD(P)HX increases, and in the absence of repair, NAD(P)H is depleted, and NAD(P)HX accumulates, leading to decompensation; however, the contribution of each to the metabolic derangement is not established. Herein, we summarize the clinical knowledge of NAXE deficiency from 30 cases and lessons learned about disease pathogenesis from cell cultures and model organisms and describe a metabolomics signature obtained by untargeted metabolomics analysis in one case at the time of crisis and after initiation of treatment. Overall, biochemical findings support a model of acute depletion of NAD, signs of mitochondrial dysfunction, and altered lipidomics. These findings are further substantiated by untargeted metabolomics six months post-crisis showing that niacin supplementation reverses primary metabolomic abnormalities concurrent with improved clinical status.
Topics: Animals; Humans; Metabolic Diseases; NAD; NADP; Racemases and Epimerases
PubMed: 35637064
DOI: 10.1016/j.ymgme.2022.04.003 -
Texas Medical Journal (Austin, Tex.) May 1916
PubMed: 36957179
DOI: No ID Found -
Bioscience of Microbiota, Food and... 2022Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We...
Pellagra is caused by an abnormal intake and/or use of niacin, but its phenotypes are diverse. The phenotypes of pellagra can also be atypical, such as nausea. We previously reported a mouse model of pellagra-related nausea. However, the mechanism of this model is unclear. In this study, we found that the gut microbiota, which is thought to be a source of niacin, played an important role in the development of pellagra-related nausea in germ-free mice. We also investigated the gut microbiome. We compared urinary niacin metabolite levels and the dermal response between mice fed a normal diet and those fed a low-niacin diet to investigate the putative trigger of pellagra. Epoxyeicosatrienoic and hydroxyeicosatetraenoic acid levels were higher in mice fed a low-niacin diet compared with those fed a normal diet. Furthermore, histological studies indicated a dermatological response to the low-niacin diet. Interestingly, higher levels of oxidised fatty acids in response to the germ-free state were also observed. These findings indicate successful establishment of our newly established mouse model of pellagra via the gut microbiota. We believe that this model could enable the discovery of the putative cause of pellagra and phenotypes of pellagra that have not been recognised yet.
PubMed: 35433165
DOI: 10.12938/bmfh.2021-059 -
European Journal of Case Reports in... 2022Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae....
UNLABELLED
Suboptimal nutrition can lead to deficiencies in micronutrients such as ascorbic acid (vitamin C), which can present with catastrophic neurological sequelae. Deficiencies of vitamin C, vitamin B3 (niacin) and zinc levels contribute to reduced bone density. Vitamin C associated vertebral fractures, although rare in adults, are still treatable if diagnosed early with a thorough clinical and nutritional history, and early supplementation. Radiological clues suggestive of scurvy-induced vertebral fractures can be diagnosed on plain X-ray and MRI spine imaging.
LEARNING POINTS
Although nutritional deficits like scurvy, pellagra and zinc deficiency are rare, early recognition and prompt treatment can prevent critical neurological sequelae.Clinical history including nutritional intake and associated patient symptoms are vital to diagnose scurvy-related vertebral fractures, which are treatable.It is important to note that scurvy can also present in an adult population.
PubMed: 36506738
DOI: 10.12890/2022_003359 -
Southern African Journal of HIV Medicine 2017Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria...
Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible.
PubMed: 29568622
DOI: 10.4102/sajhivmed.v18i1.676 -
Hellenic Journal of Nuclear Medicine 2023The carcinoid syndrome (CS) is a constellation of symptoms attributed to hypersecretion of amines, prostaglandins and polypeptides. The cardinal symptoms of CS are...
The carcinoid syndrome (CS) is a constellation of symptoms attributed to hypersecretion of amines, prostaglandins and polypeptides. The cardinal symptoms of CS are flushing, diarrhea and bronchospasm; however, CS may present with various symptoms and signs, as: Skin: cutaneous flushes, cyanosis, pellagra, Gastrointestinal: diarrhea, nausea, abdominal cramps, vomiting, Heart: tricuspid and pulmonic valve thickening causing right heart failure, edema, Respiratory: wheezing, dyspnea.
Topics: Humans; Carcinoid Heart Disease; Malignant Carcinoid Syndrome; Diarrhea; Carcinoid Tumor
PubMed: 37658565
DOI: No ID Found