|Systematic IUPAC name
|Jmol 3D model||Interactive image
|Molar mass||123.1094 g mol−1|
|Appearance||White, translucent crystals|
|Density||1.473 g cm−3|
|Melting point||237 °C; 458 °F; 510 K|
|18 g L−1|
Refractive index (nD)
Std enthalpy of
|−344.9 kJ mol−1|
Std enthalpy of
|−2.73083 MJ mol−1|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Niacin (also known as vitamin B3 or nicotinic acid) is an organic compound with the formula C
2 and, depending on the definition used, one of the 20 to 80 essential human nutrients. Pharmaceutical and supplemental niacin are primarily used to treat hypercholesterolemia (high cholesterol) and pellagra (niacin deficiency). Insufficient niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches, and tiredness. The lack of niacin may also be observed in pandemic deficiency disease, which is caused by a lack of five crucial vitamins (niacin, vitamin C, thiamin, vitamin D, and vitamin A) and is usually found in areas of widespread poverty and malnutrition. Niacin has not been found to be useful in decreasing the risk of cardiovascular disease in those already on a statin but appears to be effective in those not taking a statin.
This colorless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide and nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH
2), as well as more complex amides and a variety of esters. Nicotinic acid and niacinamide are convertible to each other with steady world demand rising from 8,500 tonnes per year in the 1980s to 40,000 in recent years.
Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in vivo. NAD converts to NADP by phosphorylation in the presence of the enzyme NAD+ kinase. NADP and NAD are coenzymes for many dehydrogenases, participating in many hydrogen transfer processes. NAD is important in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in anabolism reactions such as fatty acid and cholesterol synthesis. High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency. Although the two are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects (lipid modifying effects) as niacin. Nicotinamide does not reduce cholesterol or cause flushing. Niacin is involved in both DNA repair and the production of steroid hormones in the adrenal gland.
- 1 Dietary needs
- 2 Deficiency
- 3 Medical uses
- 4 Contraindications
- 5 Adverse effects and toxicity
- 6 Pharmacology
- 7 Physical and chemical properties
- 8 Preparations
- 9 Food sources
- 10 History
- 11 References
- 12 External links
One recommended daily allowance of niacin is 2–12 mg/day for children, 14 mg/day for women, 16 mg/day for men, and 18 mg/day for pregnant or breast-feeding women. Tolerable upper intake levels (UL) for adult men and women is considered to be 35 mg/day by the Dietary Reference Intake system to avoid flushing. In general, niacin status is tested through urinary biomarkers, which are believed to be more reliable than plasma levels.
Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths. Dr. Joseph Goldberger was assigned to study pellagra by the Surgeon General of the United States and produced good results. In the late 1930s, studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin cured pellagra in humans. The disease was greatly reduced as a result.
At present, niacin deficiency is sometimes seen in developed countries, and it is usually apparent in conditions of poverty, malnutrition, and chronic alcoholism. It also tends to occur in areas where people eat maize (corn) as a staple food, since it is the only grain low in digestible niacin. A special cooking technique called nixtamalization is needed to increase the bioavailability of niacin during maize meal/flour production.
Mild niacin deficiency has been shown to slow metabolism, causing decreased tolerance to cold.
Severe deficiency of niacin in the diet causes the disease pellagra, which is characterized by diarrhea, dermatitis, and dementia, as well as “Casal's necklace” lesions on the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, amnesia, delirium, and eventually death, if left untreated. Common psychiatric symptoms of niacin deficiency include irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression. Studies have indicated that, in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition. Patients with alcoholism typically experience increased intestinal permeability, leading to negative health outcomes.
Hartnup’s disease is a hereditary nutritional disorder resulting in niacin deficiency. This condition was first identified in the 1950s by the Hartnup family in London. It is due to a deficit in the intestines and kidneys, making it difficult for the body to break down and absorb dietary tryptophan. The resulting condition is similar to pellagra, including symptoms of red, scaly rash, and sensitivity to sunlight. Oral niacin is given as a treatment for this condition in doses ranging from 40–200 mg, with a good prognosis if identified and treated early. Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor tryptophan to form serotonin.
A 2014 review of niacin did not find that it affected either cardiovascular disease or risk of death in those already taking a statin. Niacin alone appears to reduce the risk of cardiovascular disease.
The National Cholesterol Education Program (NCEP) in 2002 recommended niacin alone for cardiovascular and atherogenic dyslipidemia in mild or normal LDL levels or in combination for higher HDL levels.
Treatment of deficiency
Nicotinic acid has been also approved by the FDA for pellagra.
Nicotinic acid has been used as a topical vasodilator or skin cream. Moreover, niacin is applied topically as a lip plumper, due to its vasodilation effect. The vasodilated lips are slightly swollen and redder, making them appear "full-blooming," which is typically desired.
Niacin is contraindicated with active liver disease, persistent elevated serum transaminases, active peptic ulcer disease, or arterial bleeding.
Adverse effects and toxicity
The most common adverse effects are flushing (e.g., warmth, redness, itching and/or tingling), headache, pain, abdominal pain, diarrhea, dyspepsia, nausea, vomiting, rhinitis, pruritus and rash. These can be minimized by initiating therapy at low dosages, increasing dosage gradually, and avoiding administration on an empty stomach.
Pharmacological doses of niacin (1.5 – 6 g per day) lead to side effects that can include dermatological conditions such as skin flushing and itching, dry skin, and skin rashes including eczema exacerbation and acanthosis nigricans.
Flushing usually lasts for about 15 to 30 minutes, though it can sometimes last up to two hours. It is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. Flushing can be blocked by taking 300 mg of aspirin half an hour before taking niacin, by taking one tablet of ibuprofen per day or by co-administering the prostaglandin receptor antagonist laropiprant. Taking niacin with meals also helps reduce this side effect. Acquired tolerance will also help reduce flushing; after several weeks of a consistent dose, most patients no longer experience flushing. Reduction of flushing focuses on altering or blocking the prostaglandin mediated pathway. Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects. One study showed the incidence of flushing was significantly lower with a sustained-release formulation, though doses above 2 g per day have been associated with liver damage, in particular, with slow-release formulations.
Prostaglandin (PGD2) is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction. The effect is mediated by prostaglandin E2 and D2 due to GPR109A activation of epidermal Langerhans cells and keratinocytes. Langerhans cells use cyclooxygenase type 1 (COX-1) for PGE2 production and are more responsible for acute flushing, while keratinocytes are COX-2 dependent and are in active continued vaso-dilation. Flushing was often thought to involve histamine, but histamine has been shown not to be involved in the reaction.
Gastrointestinal and hepatic
Gastrointestinal complaints, such as dyspepsia (indigestion), nausea and liver toxicity fulminant hepatic failure, have also been reported. Hepatotoxicity is possibly related to metabolism via amidation resulting in NAD production. The time-release form has a lower therapeutic index for lowering serum lipids relative to this form of toxicity.
Although high doses of niacin may elevate blood sugar, thereby worsening diabetes mellitus, recent studies show the actual effect on blood sugar to be only 5–10%. Patients with diabetes who continued to take anti-diabetes drugs containing niacin did not experience major blood glucose changes. Thus overall, niacin continues to be recommended as a drug for preventing cardiovascular disease in patients with diabetes.
Side effects of cardiac arrhythmias have also been reported.[page needed] Increased PT and decreased platelet count have been reported, therefore these should be monitored closely in patients who are also taking anticoagulants.
Particularly the time-release variety, at extremely high doses, can cause acute toxic reactions. Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina, which leads to blurred vision and blindness. This maculopathy is reversible after niacin intake ceases.
Niacin therapeutic effect is mostly through its binding to G protein coupled receptors, niacin receptor 1 (NIACR1) and niacin receptor 2 (NIACR2), that are highly expressed in adipose tissue, spleen, immune cells and keratinocytes but not in other expected organs such as liver, kidney, heart or intestine. A carboxyl group of nicotinic acid is a crucial moiety for the binding in which both oxygen atoms of the carboxyl group can bind to positively charged residue of arginine 111 of transmembrane helices (TMH) 3 via electrostatic interaction. Moreover, nitrogen atom of pyridine ring of nicotinic acid interacts with serine 178 of extracellular loop (ECL) 2 by embedding between TMH2/ECL1 junction and TMH7. NIACR1 and NIACR2 inhibit cyclic adenosine monophosphate (cAMP) production and thus fat breakdown in adipose tissue and free fatty acids available for liver to produce triglycerides and very-low-density lipoproteins (VLDL) and consequently low-density lipoprotein (LDL) or "bad" cholesterol. Decrease in free fatty acids also suppress hepatic expression of apolipoprotein C3 (APOC3) and PPARg coactivator-1b (PGC-1b) thus increase VLDL turn over and reduce its production. It also inhibits diacylglycerol acyltransferase-2 (important hepatic TG synthesis).
The mechanism behind increasing HDL is not totally understood but it seems to be done in various ways. Niacin increases apolipoprotein A1 levels due to anti catabolic effects resulting in higher reverse cholesterol transport. It also inhibits HDL hepatic uptake, down-regulating production of the cholesterol ester transfer protein (CETP) gene. Finally, it stimulates the ABCA1 transporter in monocytes and macrophages and up-regulates peroxisome proliferator-activated receptor γ results in reverse cholesterol transport.
It reduces secondary outcomes associated with atherosclerosis, such as low density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), but increases high density lipoprotein cholesterol (HDL). Despite the importance of other cardiovascular risk factors, high HDL was associated with fewer cardiovascular events independent of LDL reduction. Other effects include anti-thrombotic and vascular inflammation, improving endothelial function, and plaque stability. Adipokines are the adipocytes’ produced mediators. Some adipokines such as tumor necrosis factor (TNF)-a, interleukins and chemokines, have pro-inflammatory effect and some others such as adiponectin have anti-inflammatory effect that regulates inflammatory process, decrease vascular progression and atherosclerosis.
Research has been able to show the function of niacin in the pathway lipid metabolism. It is seen that this vitamin can decrease the synthesis of apoB-containing lipoproteins such as VLDL, LDL, IDL and Lipoprotein (a) via several mechanisms: (1) Directly inhibiting the action of DGAT2, a key enzyme for triglyceride synthesis; (2) It has the ability to bind to the receptor HCAR2 thereby decreasing lipolysis and FFA flux to the liver for triglyceride synthesis; and (3) increased apoB catabolism. On the other hand, HDL cholesterol levels are increased by niacin through direct and indirect pathways. (4) Niacin decreases CETP mass and activity, and this synergistic effect with the decrease in triglyceride levels, can indirectly raise HDL cholesterol levels. The study has also been able to show direct effects on the beta chain of ATP synthase (5) and on production (6) and hepatic uptake (7) of apoA-I also increase HDL cholesterol levels. Thus by affecting the pathway reducing lipid levels help in reducing CVD.
This section requires expansion. (September 2015)
The liver can synthesize niacin from the essential amino acid tryptophan, requiring 60 mg of tryptophan to make one mg of niacin. Riboflavin, vitamin B6 and iron are required in some of the reactions involved in the conversion of tryptophan to NAD.
Physical and chemical properties
Several thousand tons of niacin are manufactured each year, starting from 3-methylpyridine.
Many preparations of niacin are available over-the-counter as dietary supplements. Non-prescription extended release niacin, such as Endur-acin, which uses a wax matrix to delay release is available as well.
Over-the counter plain niacin has FDA regulatory approval. Some “no flush” types, such as inositol hexanicotinate contain convertible niacin compounds, but have little clinical efficacy in reducing cholesterol levels. “Slow release” varieties have higher hepatotoxic activity, hence some types of prescription niacin are not recommended due to potential harm.
A prescription extended release niacin, Niaspan, has a film coating that delays release of the niacin, resulting in an absorption over a period of 8–12 hours. The extended release formulations generally reduce vasodilation and flushing side effects, but increase the risk of hepatotoxicity compared to the immediate release forms.
A formulation of laropiprant (Merck & Co., Inc.) and niacin had previously been approved for use in Europe and marketed as Tredaptive. Laropiprant is a prostaglandin D2 binding drug shown to reduce vasodilatation and flushing up to 73%. The HPS2-THRIVE study, a study sponsored by Merck, showed no additional efficacy of Tredaptive in lowering cholesterol when used together with other statin drugs, but did show an increase in other side effects. The study resulted in the complete withdrawal of Tredaptive from the international market.
One form of dietary supplement is inositol hexanicotinate (IHN), which is inositol that has been esterified with niacin on all six of inositol's alcohol groups. IHN is usually sold as "flush-free" or "no-flush" niacin in units of 250, 500, or 1000 mg/tablets or capsules. It is sold as an over-the-counter formulation, and often is marketed and labeled as niacin, thus misleading consumers into thinking they are getting the active form of the medication. While this form of niacin does not cause the flushing associated with the immediate-release products, the evidence that it has lipid-modifying functions is contradictory, at best. As the clinical trials date from the early 1960s (Dorner, Welsh) or the late 1970s (Ziliotto, Kruse, Agusti), it is difficult to assess them by today's standards. One of the last of those studies affirmed the superiority of inositol and xantinol esters of nicotinic acid for reducing serum free fatty acid, but other studies conducted during the same period found no benefit. Studies explain that this is primarily because "flush-free" preparations do not contain any free nicotinic acid. A more recent placebo-controlled trial was small (n=11/group), but results after three months at 1500 mg/day showed no trend for improvements in total cholesterol, LDL-C, HDL-C or triglycerides. Thus, so far there is not enough evidence to recommend IHN to treat dyslipidemia.
Nicotinamide may be obtained from the diet where it is present primarily as NAD+ and NADP+. These are hydrolysed in the intestine and the resulting nicotinamide is absorbed either as such, or following its hydrolysis to nicotinic acid. Nicotinamide is present in nature in only small amounts. In unprepared foods, niacin is present mainly in the form of the cellular pyridine nucleotides NAD and NADP. Enzymatic hydrolysis of the co-enzymes can occur during the course of food preparation. Boiling releases most of the total niacin present in sweet corn as nicotinamide (up to 55 mg/kg).
Nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.
Niacin is found in variety of foods, including liver, chicken, beef, fish, cereal, peanuts, and legumes, and is also synthesized from tryptophan, an essential amino acid found in most forms of protein.
- liver, heart and kidney (9 – 15 mg niacin per 100 grams)
- chicken, chicken breast (6.5 mg)
- beef (5 – 6 mg)
- fish: tuna, salmon, halibut (2.5 – 13 mg)
- eggs (0.1 mg)
- venison (8.43 mg)
Fruits and vegetables:
- avocados (1 mg niacin per 100 grams)
- dates (2 mg)
- tomatoes (0.7 mg)
- leaf vegetables (0.3 – 0.4 mg)
- broccoli (0.6 mg)
- carrots (0.3 – 0.6 mg)
- sweet potatoes (0.5 – 0.6 mg)
- asparagus (0.4 mg)
- nuts (2 mg niacin per 100 grams)
- whole grain products (4 – 29.5 mg)
- legumes (0.4 – 16 mg)
- saltbush seeds
- beer (6 mg per pint, less if filtered)
- Ovaltine (18 mg)
- Peanut butter (15 mg)
- Soy sauce (0.4 mg)
- Vegemite (from spent brewer's yeast) (50 mg niacin per 100 grams)
- Marmite (from spent brewer's yeast) (50 mg niacin per 100 grams)
Niacin was first described by chemist Hugo Weidel in 1873 in his studies of nicotine. The original preparation remains useful: The oxidation of nicotine using nitric acid. For the first time, niacin was extracted by Casimir Funk, but he thought that it was thiamine and due to the discovered amine group he coined the term "vitamine". Niacin was extracted from livers by biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor." Soon after, in studies conducted in Alabama and Cincinnati, Dr. Tom Spies found that nicotinic acid cured the sufferers of pellagra.
Niacin is referred to as vitamin B3 because it was the third of the B vitamins to be discovered. It has historically been referred to as "vitamin PP", "vitamin P-P" and "PP-factor", that are derived from the term "pellagra-preventive factor". When the biological significance of nicotinic acid was realized, it was thought appropriate to choose a name to dissociate it from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name 'niacin' was derived from nicotinic acid + vitamin.
In 1955, Altschul and colleagues described niacin as having a lipid lowering property. Niacin is the oldest lipid lowering drug.
On April 22, 2014, Pennsylvania State University researchers working with NASA at the Goddard Astrobiology Analytical Laboratory reported of finding niacin within eight CM-2 type carbonaceous chondrite meteorites. The meteorite’s vitamin B3 levels ranged from 30–600 parts per billion, the study reports. Related molecules discovered in the meteorites include pyridine carboxylic acids and pyridine dicarboxylic acids.
- "Niacin". DrugBank: a knowledgebase for drugs, drug actions and drug targets. Retrieved 14 January 2012.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- CID 938 from PubChem
- Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
- Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
- Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
- Cox, Michael; Lehninger, Albert L; Nelson, David R. (2000). Lehninger principles of biochemistry. New York: Worth Publishers. ISBN 1-57259-153-6. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Jacobson, EL (2007). "Niacin". Linus Pauling Institute. Retrieved 8 August 2011.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Institute of Medicine (2006). Dietary Reference Intakes Research Synthesis: Workshop Summary. National Academies Press. p. 37.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Jacob RA, Swendseid ME, McKee RW, Fu CS, Clemens RA (April 1989). "Biochemical markers for assessment of niacin status in young men: urinary and blood levels of niacin metabolites". J. Nutr. 119 (4): 591–8. PMID 2522982. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- NCEP (2002). "Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report". Circulation. 106 (25): 3143–3421.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Kos Pharmaceuticals Inc. Niaspan® (niacin extended-release) tablets prescribing information. Cranbury, NJ; 2005 Oct.
- "Guidelines for Niacin Therapy For the Treatment of Elevated Lipoprotein a (Lpa)" (PDF). Rush Hemophilia & Thrombophilia Center. 27 July 2005 [15 August 2002]. Retrieved 20 November 2009.
facial flushing is a common side effect of niacin therapy that usually subsides after several weeks of consistent niacin use<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Katzung, Bertram G. (2006). Basic and clinical pharmacology. New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Brunton, Laurence L.; Lazo, John S.; Parker, Keith, eds. (2005). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. ISBN 0-07-142280-3.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Gass JD (2003). "Nicotinic acid maculopathy". Retina (Philadelphia, Pa.). 23 (6 Suppl): 500–10. PMID 15035390.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Jacobson, EL (2007). "Niacin". Linus Pauling Institute. Retrieved 31 March 2008.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Endur-Acin Oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD
- L-arginine, niacin, phytosterols, pantethine, calcium, vitamin c, b complex, cholesterol control without diet, 8 week cholesterol cure, linus pauling
- Study Finds Extended Release Niacin, but not IHN, Effective in Lowering Cholesterol Levels
- Pharmacokinetics and dose recommendations of Niaspan® in chronic kidney disease and dialysis patients
- Niaspan (Niacin) Drug Information: Description, User Reviews, Drug Side Effects, Interactions – Prescribing Information at RxList
- About NIASPAN® (niacin extended-release)
- Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value)..
- Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE – Full Text View – ClinicalTrials.gov
- Medscape: Medscape Access
- "Merck begins overseas recall of HDL cholesterol drug". Reuters. 11 January 2013.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Taheri, R (15 January 2003). "No-Flush Niacin for the Treatment of Hyperlipidemia". Medscape. Retrieved 31 March 2008.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- F. Aguilar, U.R. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Guertler, G.E.N. Kass, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen (2009). "Inositol hexanicotinate (inositol hexaniacinate) as a source of niacin (vitamin B3) added for nutritional purposes in food supplements" (PDF). The EFSA Journal. 949: 1–20. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Diet & Fitness today. "Niacin in beer".<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- "Vegemite – Nutritional information". Retrieved 6 November 2013.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- "Marmite – Nutritional information". Retrieved 19 November 2014.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Samuel M. McElvain (1941). "Nicotinic Acid" (PDF). Org. Synth.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>; Coll. Vol., 1, p. 385<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Elvehjem CA, Madden RJ, Strongandd FM, Woolley DW (1938). "The isolation and identification of the anti-blacktongue factor J" (PDF). J. Biol. Chem. 123 (1): 137–149. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Dr. Joseph Goldberger and the war on Pellagra – Office of NIH History
- "Pellagra And Its Prevention And Control In Major Emergencies" (PDF). World Health Organization. World Health Organization. Retrieved 17 April 2015.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Laguna J, Carpenter KJ (September 1951). "Raw versus processed corn in niacin-deficient diets". J. Nutr. 45 (1): 21–8. PMID 14880960.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
- Vitamins B3 found in Meteorites http://canadajournal.net/science/vitamins-b3-found-meteorites-study-6534-2014/