Editing Niacin (section)

==Vitamin deficiency==
{{Main|Pellagra}}
[[File:Pellagra2.jpg|thumb|left|A man with [[pellagra]], which is caused by a chronic lack of vitamin B<sub>3</sub> in the diet]]

Severe deficiency of niacin in the diet causes the disease [[pellagra]], characterized by [[diarrhea]], sun-sensitive [[dermatitis]] involving hyperpigmentation and thickening of the skin (see image), inflammation of the mouth and tongue, delirium, dementia, and if left untreated, death.<ref name=Hegyi2004 /> Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, loss of memory, restlessness, apathy, and depression.<ref name=PKIN2020Niacin /> The biochemical mechanism(s) for the observed deficiency-caused neurodegeneration are not well understood, but may rest on: A) the requirement for [[nicotinamide adenine dinucleotide]] (NAD+) to suppress the creation of neurotoxic tryptophan metabolites, B) inhibition of mitochondrial ATP generation, resulting in cell damage; C), activation of the [[poly (ADP-ribose) polymerase]] (PARP) pathway, as PARP is a nuclear enzyme involved in DNA repair, but in the absence of NAD+ can lead to cell death; D) reduced synthesis of neuro-protective [[brain-derived neurotrophic factor]] or its receptor [[tropomyosin receptor kinase B]]; or E) changes to genome expression directly due to the niacin deficiency.<ref name="niacin review 2014">{{cite journal | vauthors = Fu L, Doreswamy V, Prakash R | title = The biochemical pathways of central nervous system neural degeneration in niacin deficiency | journal = Neural Regeneration Research | volume = 9 | issue = 16 | pages = 1509–13 | date = August 2014 | pmid = 25317166 | pmc = 4192966 | doi = 10.4103/1673-5374.139475 | doi-access = free }}</ref>

Niacin deficiency is rarely seen in developed countries, and it is more typically associated with poverty, malnutrition or malnutrition secondary to chronic [[alcoholism]].<ref>{{cite journal |vauthors = Pitsavas S, Andreou C, Bascialla F, Bozikas VP, Karavatos A |s2cid = 29070525 |title = Pellagra encephalopathy following B-complex vitamin treatment without niacin |journal = International Journal of Psychiatry in Medicine |volume = 34 |issue = 1 |pages = 91–5 |date = March 2004 |pmid = 15242145 |doi = 10.2190/29XV-1GG1-U17K-RGJH |url = http://baywood.metapress.com/link.asp?id=29xv1gg1u17krgjh |access-date = 27 November 2009 |archive-url = https://archive.today/20120710191340/http://baywood.metapress.com/link.asp?id=29xv1gg1u17krgjh |archive-date = 10 July 2012 |url-status = dead }}</ref> It also tends to occur in less developed areas where people eat [[maize]] (corn) as a staple food, as maize is the only grain low in digestible niacin. A cooking technique called [[nixtamalization]] i.e., pretreating with alkali ingredients, increases the bioavailability of niacin during maize meal/flour production.<ref>{{cite journal |vauthors=Bressani R, Gomez-Brenes R, Scrimshaw NS |title=Effect of processing on distribution and in vitro availability of niacin of corn (Zea mays) |journal=Food Technol|date=1961 |volume=15 |pages=450–4 }}</ref> For this reason, people who consume maize as tortillas or [[hominy]] are at less risk of niacin deficiency.

For treating deficiency, the World Health Organization (WHO) recommends administering nicotinamide, instead of nicotinic acid, to avoid the flushing side effect commonly caused by the latter. Guidelines suggest using 300&nbsp;mg/day for three to four weeks.<ref name="Pellagra And Its Prevention" /> Dementia and dermatitis show improvement within a week. Because deficiencies of other B-vitamins may be present, the WHO recommends a multi-vitamin in addition to the nicotinamide.<ref name="Pellagra And Its Prevention" />

[[Hartnup disease]] is a [[hereditary]] nutritional disorder resulting in niacin deficiency.<ref name=HartnupMerck>{{cite web |url=https://www.merckmanuals.com/professional/pediatrics/congenital-renal-transport-abnormalities/hartnup-disease?query=Hartnup%20Disease |title=Hartnup Disease |vauthors=LaRosa CJ |date=January 2020 |access-date=6 July 2020 |archive-date=8 July 2020 |archive-url=https://web.archive.org/web/20200708204521/https://www.merckmanuals.com/professional/pediatrics/congenital-renal-transport-abnormalities/hartnup-disease?query=Hartnup%20Disease |url-status=dead }}</ref> It is named after an English family with a genetic disorder that resulted in a failure to absorb the essential amino acid [[tryptophan]], tryptophan being a precursor for niacin synthesis. The symptoms are similar to pellagra, including red, scaly rash and sensitivity to sunlight. Oral nicotinic acid or nicotinamide is given as a treatment for this condition in doses ranging from 50 to 100&nbsp;mg twice a day, with a good prognosis if identified and treated early.<ref name=HartnupMerck /> Niacin synthesis is also deficient in [[carcinoid syndrome]], because of metabolic diversion of its [[precursor (chemistry)|precursor]] [[tryptophan]] to form [[serotonin]].<ref name="lpi" />

===Measuring vitamin status===
Plasma concentrations of niacin and niacin metabolites are not useful markers of niacin status.<ref name="DRItext"/> Urinary excretion of the methylated metabolite N1-methyl-nicotinamide is considered reliable and sensitive. The measurement requires a 24-hour urine collection. For adults, a value of less than 5.8 μmol/day represent deficient niacin status and 5.8 to 17.5 μmol/day represents low.<ref name="DRItext"/> According to the World Health Organization, an alternative mean of expressing urinary N1-methyl-nicotinamide is as mg/g creatinine in a 24-hour urine collection, with deficient defined as <0.5, low 0.5-1.59, acceptable 1.6-4.29, and high >4.3<ref name="Pellagra And Its Prevention" /> Niacin deficiency occurs before the signs and symptoms of pellagra appear.<ref name="DRItext"/> Erythrocyte [[nicotinamide adenine dinucleotide]] (NAD) concentrations potentially provide another sensitive indicator of niacin depletion, although definitions of deficient, low and adequate have not been established. Lastly, plasma [[tryptophan]] decreases on a low niacin diet because tryptophan converts to niacin. However, low tryptophan could also be caused by a diet low in this essential [[amino acid]], so it is not specific to confirming vitamin status.<ref name="DRItext"/>