Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms, or vitamers: nicotinic acid (niacin), nicotinamide (niacinamide), and nicotinamide riboside.[1][2] All three forms of vitamin B3 are converted within the body to nicotinamide adenine dinucleotide (NAD).[1][3] NAD is required for human life and people are unable to make it within their bodies without either vitamin B3 or tryptophan.[1] Nicotinamide riboside was identified as a form of vitamin B3 in 2004.[2][4]
Niacin (the nutrient) can be manufactured by plants and animals from the amino acid tryptophan.[5] Niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortifiedpackaged foods, meat, poultry, red fish such as tuna and salmon, lesser amounts in nuts, legumes and seeds.[1][3] Niacin as a dietary supplement is used to treat pellagra, a disease caused by niacin deficiency. Signs and symptoms of pellagra include skin and mouth lesions, anemia, headaches, and tiredness.[1][6] Many countries mandate its addition to wheat flour or other food grains, thereby reducing the risk of pellagra.[3][7]
Example of a label showing the amount of niacin (Vitamin B3), and specifying to be niacinamide in the ingredient section.
The United States Government adopted the terms niacin and niacinamide in 1942 as alternate names for nicotinic acid and nicotinamide, respectively, and encouraged their use in nontechnical contexts to avoid the public’s confusing them with the nearly unrelated (and toxic) nicotine.[12][13] The terms were incorporated into the United States Adopted Name dictionary [14] that was created in 1961.[15]
The term niacin was then adopted internationally by multiple institutions (WHO/FAO,[16]EFSA,[17]FDA,[18]Anvisa[19]) using a broader meaning including all dietary NAD precursors that can prevent signs of deficiency. In other words, the term is used with the same meaning as vitamin B3, including not just nicotinic acid, but also nicotinamide, and nicotinamide riboside.[20][21][22]
A man with pellagra, which is caused by a chronic lack of vitamin B3 in the diet
Severe vitamin B3 deficiency 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.[6] Common psychiatric symptoms include irritability, poor concentration, anxiety, fatigue, loss of memory, restlessness, apathy, and depression.[24] The biochemical mechanisms 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.[25]
Niacin deficiency is rarely seen in developed countries, and it is more typically associated with poverty, malnutrition or malnutrition secondary to chronic alcoholism.[26] It also tends to occur in areas where people eat maize (corn) as a staple food, as maize is low in digestible niacin.[1] A cooking technique called nixtamalization, that is, pretreating with alkali ingredients, increases the bioavailability of niacin during maize meal or flour production.[27] For this reason, people who consume corn 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 300mg/day for three to four weeks.[10] 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.[10]
Hartnup disease is a hereditary nutritional disorder resulting in niacin deficiency.[28] It is named after an English family with a genetic disorder that resulted in a failure to absorb the essential amino acidtryptophan, 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 100mg twice a day, with a good prognosis if identified and treated early.[28] Niacin synthesis is also deficient in carcinoid syndrome, because of metabolic diversion of its precursor tryptophan to form serotonin.[3]
Measuring vitamin status
Plasma concentrations of niacin and niacin metabolites are not useful markers of niacin status.[5] 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.[5] 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[10] Niacin deficiency occurs before the signs and symptoms of pellagra appear.[5] 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 nicotinic acid mononucleotide (NaMN) and then to NAD by the kynurenine pathway.[29] 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.[5]
* Adequate intake for infants, as an RDA has yet to be established ** Not possible to establish; source of intake should be formula and food only[5]
The U.S. Institute of Medicine (renamed National Academy of Medicine in 2015) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for niacin in 1998, as well as Tolerable upper intake levels (ULs). In lieu of an RDA, Adequate Intakes (AIs) are identified for populations for which there is not enough evidence to identify a dietary intake level that is sufficient to meet the nutrient requirements of most people.[33] (see table).
The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values (DRV), with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. For the EU, AIs and ULs have the same definition as in the US, except that units are milligrams per megajoule (MJ) of energy consumed rather than mg/day. For women (including those pregnant or lactating), men and children the PRI is 1.6mg per megajoule. As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories should be consuming 16mg niacin. This is comparable to US RDAs (14mg/day for adult women, 16mg/day for adult men).[34]
ULs are established by identifying amounts of vitamins and minerals that cause adverse effects, and then selecting as an upper limit amounts that are the "maximum daily intake unlikely to cause adverse health effects".[33] Regulatory agencies from different countries do not always agree. For the US, 30 or 35mg of niacin for teenagers and adults, less for children.[5] The EFSA UL for adults is set at 10mg/day for nicotinic acid to avoid the skin flush reaction, and 900mg/day for nicotinamide that doesn't cause flushing.[32]
Both the DRI and DRV describe amounts needed as niacin equivalents (NE), calculated as 1mg NE = 1mg niacin or 60mg of the essential amino acid tryptophan. This is because the amino acid is utilized to synthesize the vitamin.[5][34]
For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For niacin labeling purposes 100% of the Daily Value is 16mg. Prior to May 27, 2016, it was 20mg, revised to bring it into agreement with the RDA.[35][36] Compliance with the updated labeling regulations was required by January 1, 2020, for manufacturers with US$10million or more in annual food sales, and by January 1, 2021, for manufacturers with lower volume food sales.[37][38] A table of the old and new adult daily values is provided at Reference Daily Intake.
Sources
Niacin is found in a variety of whole and processed foods, including fortifiedpackaged foods, meat from various animal sources, seafoods, and spices.[3][39] In general, animal-sourced foods provide about 5–10mg niacin per serving, although dairy foods and eggs have little. Some plant-sourced foods such as nuts, legumes and grains provide about 2–5mg niacin per serving, although in some grain products this naturally present niacin is largely bound to polysaccharides and glycopeptides, making it only about 30% bioavailable. Fortified food ingredients such as wheat flour have niacin added, which is bioavailable.[1] Among whole food sources with the highest niacin content per 100 grams:
Vegetarian and vegan diets can provide adequate amounts if products such as nutritional yeast, peanuts, peanut butter, tahini, brown rice, mushrooms, avocado and sunflower seeds are included. Fortified foods and dietary supplements can also be consumed to ensure adequate intake.[1][42]
Food preparation
Niacin naturally found in food is susceptible to destruction from high heat cooking, especially in the presence of acidic foods and sauces. It is soluble in water, and so may also be lost from foods boiled in water.[43]
Food fortification
Countries fortify foods with nutrients to address known deficiencies.[7] As of 2020, 54 countries required food fortification of wheat flour with nicotinic acid or nicotinamide; 14 also mandate fortification of maize flour, and 6 mandate fortification of rice.[44] From country to country, niacin fortification ranges from 1.3 to 6.0mg/100 g.[44]
As a dietary supplement
In the United States, nicotinic acid is sold as a non-prescription dietary supplement with a range of 100 to 1000mg per serving. These products often have a Structure/Function health claim[45] allowed by the US Food & Drug Administration (FDA). An example would be "Supports a healthy blood lipid profile." The American Heart Association (AHA) strongly advises against the use of non-prescription dietary supplement nicotinic acid rather than prescription nicotinic acid because of potentially serious side effects. For this reason and because the manufacture of dietary supplement nicotinic acid is not as well-regulated by the FDA as is prescription nicotinic acid, the AHA advises that supplemental nicotinic acid only be used under the supervision of a health care professional.[46] More than 30mg nicotinic acid consumed as a dietary supplement can cause skin flushing. Face, arms and chest skin turns a reddish color because of vasodilation of small subcutaneous blood vessels, accompanied by sensations of heat, tingling and itching. These signs and symptoms are typically transient, lasting minutes to hours; they are considered unpleasant rather than toxic.[1]
Toxicity
The US Food and Nutrition Board has set a daily limit of 35mg for vitamin B3, unless under medical supervision.[1] At daily doses of nicotinic acid as low as 30mg, flushing has been reported, always starting in the face and sometimes accompanied by skin dryness, itching, paresthesia, and headache.[23] (These effects do not occur with nicotinamide).[1] Liver toxicity is the most serious toxic reaction and it occurs at doses >2 grams/day,[47] and is possible with either nicotinic acid or nicotinamide.[1]Fulminant hepatitis has been reported at doses between 3-9 grams/day with needs for liver transplantation.[citation needed] Other reactions include glucose intolerance, hyperuricemia, macular edema, and macular cysts.[23]
Corn (maize) became a staple food in the southeast United States and in parts of Europe. A disease that was characterized by dermatitis of sunlight-exposed skin was described in Spain in 1735 by Gaspar Casal. He attributed the cause to poor diet.[48] In northern Italy it was named pellagra from the Lombard language (agra = holly-like or serum-like; pell = skin).[49][50] In time, the disease was more closely linked specifically to corn.[51] In the US, Joseph Goldberger was assigned to study pellagra by the Surgeon General of the United States. His studies confirmed a corn-based diet as the culprit, but he did not identify the root cause.[52][53]
Nicotinic acid was extracted from the liver by biochemistConrad Elvehjem in 1937. He later identified the active ingredient, referring to it as "pellagra-preventing factor" and the "anti-blacktongue factor."[54] It was also referred to as "vitamin PP", "vitamin P-P" and "PP-factor", all derived from the term "pellagra-preventive factor".[10] In the late 1930s, studies by Tom Douglas Spies, Marion Blankenhorn, and Clark Cooper confirmed that niacin cured pellagra in humans. The prevalence of the disease was greatly reduced as a result.[55]
In 1942, when flour enrichment with nicotinic acid began, a headline in the popular press said "Tobacco in Your Bread." In response, the Council on Foods and Nutrition of the American Medical Association approved of the Food and Nutrition Board's new names niacin and niacin amide for use primarily by non-scientists. It was thought appropriate to choose a name to dissociate nicotinic acid from nicotine, to avoid the perception that vitamins or niacin-rich foods contain nicotine, or that cigarettes contain vitamins. The resulting name niacin was derived from nicotinic acid + vitamin.[12][13]
J. Laguna and K.J. Carpenter found in 1951, that niacin in corn is biologically unavailable and can be released only in very alkaline lime water of pH 11. This explains why a Latin-American culture that used alkali-treated (nixtamalized) cornmeal to make tortilla was not at risk for niacin deficiency.[56]
Related Research Articles
Nicotinamide (INN, BAN UK) or niacinamide (USAN US) is a form of vitamin B3 found in food and used as a dietary supplement and medication. As a supplement, it is used orally (swallowed by mouth) to prevent and treat pellagra (niacin deficiency). While nicotinic acid (niacin) may be used for this purpose, nicotinamide has the benefit of not causing skin flushing. As a cream, it is used to treat acne, and has been observed in clinical studies to improve the appearance of aging skin by reducing hyperpigmentation and redness. It is a water-soluble vitamin.
Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement. It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. These coenzymes are involved in energy metabolism, cellular respiration, and antibody production, as well as normal growth and development. The coenzymes are also required for the metabolism of niacin, vitamin B6, and folate. Riboflavin is prescribed to treat corneal thinning, and taken orally, may reduce the incidence of migraine headaches in adults.
Vitamins are organic molecules that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in sufficient quantities for survival, and therefore must be obtained through the diet. For example, vitamin C can be synthesized by some species but not by others; it is not considered a vitamin in the first instance but is in the second. Most vitamins are not single molecules, but groups of related molecules called vitamers. For example, there are eight vitamers of vitamin E: four tocopherols and four tocotrienols.
Nicotinic acid, or niacin, is an organic compound and a vitamer ofvitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortified packaged foods, meat, poultry, red fish such as tuna and salmon, lesser amounts in nuts, legumes and seeds. Niacin as a dietary supplement is used to treat pellagra, a disease caused by niacin deficiency. Signs and symptoms of pellagra include skin and mouth lesions, anemia, headaches, and tiredness. Many countries mandate its addition to wheat flour or other food grains, thereby reducing the risk of pellagra.
Pantothenic acid (vitamin B5) is a B vitamin and an essential nutrient. All animals need pantothenic acid in order to synthesize coenzyme A (CoA), which is essential for cellular energy production and for the synthesis and degradation of proteins, carbohydrates, and fats.
Vitamin B6 is one of the B vitamins, and is an essential nutrient for humans. The term essential nutrient refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphate, serves as a coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.
A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excreted by cells to create non-cellular structures such as hair, scales, feathers, or exoskeletons. Some nutrients can be metabolically converted into smaller molecules in the process of releasing energy such as for carbohydrates, lipids, proteins and fermentation products leading to end-products of water and carbon dioxide. All organisms require water. Essential nutrients for animals are the energy sources, some of the amino acids that are combined to create proteins, a subset of fatty acids, vitamins and certain minerals. Plants require more diverse minerals absorbed through roots, plus carbon dioxide and oxygen absorbed through leaves. Fungi live on dead or living organic matter and meet nutrient needs from their host.
Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a primary deficiency, whereas when due to an underlying disorder such as malabsorption it is called a secondary deficiency. An underlying disorder can have 2 main causes:
Pellagra is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to friction and radiation are typically affected first. Over time affected skin may become darker, stiffen, peel, or bleed.
B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds.
Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids. Niacin is a precursor to nicotinamide, a necessary component of NAD+.
Conrad Arnold Elvehjem (May 27, 1901 – July 27, 1962) was internationally known as an American biochemist in nutrition. In 1937 he identified two vitamins, nicotinic acid, also known as niacin, and nicotinamide, which were deficient directly in human pellagra, once a major health problem in the United States. Collectively, nicotinic acid and nicotinamide are termed vitamin B3 and are now understood to be precursors of nicotinamide adenine dinucleotide.
Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. Megavitamin therapy is typically used in alternative medicine by practitioners who call their approach orthomolecular medicine. Vitamins are useful in preventing and treating illnesses specifically associated with dietary vitamin shortfalls, but the conclusions of medical research are that the broad claims of disease treatment by advocates of megavitamin therapy are unsubstantiated by the available evidence. It is generally accepted that doses of any vitamin greatly in excess of nutritional requirements will result either in toxicity or in the excess simply being metabolised; thus evidence in favour of vitamin supplementation supports only doses in the normal range. Critics have described some aspects of orthomolecular medicine as food faddism or even quackery. Research on nutrient supplementation in general suggests that some nutritional supplements might be beneficial, and that others might be harmful; several specific nutritional therapies are associated with an increased likelihood of the condition they are meant to prevent.
Food fortification is the addition of micronutrients to food products. Food enrichment specifically means adding back nutrients lost during food processing, while fortification includes adding nutrients not naturally present. Food manufacturers and governments have used these practices since the 1920s to help prevent nutrient deficiencies in populations. Common nutrient deficiencies in a region often result from local soil conditions or limitations of staple foods. The addition of micronutrients to staples and condiments can prevent large-scale deficiency diseases in these cases.
Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic, though compounds exist in which this is not the case. The biological functions of heterocyclic amines vary, including vitamins and carcinogens. Carcinogenic heterocyclic amines are created by high temperature cooking of meat and smoking of plant matter like tobacco. Some well known heterocyclic amines are niacin, nicotine, and the nucleobases that encode genetic information in DNA.
1-Methylnicotinamide (1-MNA,trigonellamide) is a prototypic organic cation. 1-Methylnicotinamide is the methylated amide of Nicotinamide (niacinamide, vitamin B3).
A vitamer is any of the related forms in which some vitamin occurs. Each vitamer of a particular vitamin is a compound that performs the functions of that vitamin and prevents the symptoms of deficiency of the vitamin.
Nutritional neuroscience is the scientific discipline that studies the effects various components of the diet such as minerals, vitamins, protein, carbohydrates, fats, dietary supplements, synthetic hormones, and food additives have on neurochemistry, neurobiology, behavior, and cognition.
Relatively speaking, the brain consumes an immense amount of energy in comparison to the rest of the body. The mechanisms involved in the transfer of energy from foods to neurons are likely to be fundamental to the control of brain function. Human bodily processes, including the brain, all require both macronutrients, as well as micronutrients.
Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway.
1 2 3 4 5 "Niacin". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. October 8, 2018. Retrieved September 16, 2019.
1 2 3 4 5 6 7 8 9 10 Institute of Medicine (1998). "Niacin". Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press. pp.123–149. ISBN9780309065542. Archived from the original on September 1, 2018. Retrieved August 29, 2018.
↑ International Life Sciences Institute, ed. (2012). Present knowledge in nutrition (10ed.). Oxford: Wiley-Blackwell. ISBN978-0-470-95917-6. Niacin refers to the chemical nicotinic acid, while niacinamide refers to the chemical nicotinamide. However, niacin is commonly used to refer to either form. This is unfortunate because there are significant physiological differences between niacin and niacinamide. (...) Niacin, which commonly refers to nicotinic acid or nicotinamide, is vitamin B3.
↑ Ross AC, ed. (2012). Modern nutrition in health and disease (11ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN978-1-60547-461-8.
1 2 3 Suter P, Russell R (2018). "Chapter 326: Vitamin and Trace Mineral Deficiency and Excess". Harrison's Principles of Internal Medicine, 20th Ed. New York: McGraw-Hill. ISBN9781259644030.
↑ Penberthy W, Kirkland J (2020). "Niacin". In Marriott B, Birt D, Stallings V, Yates A (eds.). Present Knowledge in Nutrition (11ed.). London, United Kingdom: Academic Press (Elsevier). pp.209–224. ISBN9780323661621.
↑ "Structure/Function Claims". U.S. Food & Drug Administration. December 2017. Archived from the original on June 10, 2020. Retrieved June 30, 2020.
↑ "Cholesterol Medications". American Heart Association. November 10, 2018. Archived from the original on April 5, 2020. Retrieved May 8, 2020.
↑ Goodman LS, Hardman JG, Limbird LE, Gilman AG (2001). Goodman & Gilman's the pharmacological basis of therapeutics (10ed.). New York: McGraw-Hill. ISBN0071354697. OCLC46548349.
↑ Casal G (1945). "The natural and medical history of the principality of the Asturias". In Major RH (ed.). Classic Descriptions of Disease (3ed.). Springfield: Charles C Thomas. pp.607–12.
↑ F. Cherubini, Vocabolario Milanese-Italiano, Imp. Regia Stamperia, 1840–43, vol. I, III.
↑ Ruth Hanna Sachs, White Rose History. Volume I. 2003. Appendix D, p. 2 ISBN978-0-9710541-9-6 "Men of the Year, outstanding in comprehensive science were three medical researchers who discovered that nicotinic acid was a cure for human pellagra: Drs. Tom Douglas Spies of Cincinnati General Hospital, Marion Arthur Blankenhorn of the University of Cincinnati, Clark Niel Cooper of Waterloo, Iowa."
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