Nicotinic acid is a vitamin that belongs to group B. It has many synonymous names: PP, nicotinamide, niacin, B3, nikonacid, pelonin, and so on. It takes an important part in the metabolism of fats, proteins and amino acids. Nicotinamide is also known for the fact that due to its absence in a person’s daily diet, the disease pellagra occurs, which most often affects the very poor and people suffering from chronic and long-term alcoholism. Classic manifestations of pellagra: dementia, diarrhea and specific dermatitis. In total, niacin is involved in 60 metabolic reactions in the body that affect energy production. For this reason, you should not neglect taking this vitamin. In principle, an unathletic and healthy person does not need additional intake of nicotinic acid, since it is independently synthesized in the body from the amino acid tryptophan. This amino acid enters the human body only with sufficient protein nutrition and produces half the daily requirement of nicotinamide. The remaining half is consumed along with the daily ration. Vegetarians must take niacin along with other vitamins.
More information about Nicotinic Acid can be found here.
Nicotinic acid (vitamin B3)[edit | edit code]
Historical background[edit | edit code]
In countries with high corn consumption, especially Italy and North America, a disease called pellagra (from the Italian relie agra, “rough skin”) has been known for centuries. In 1914, Funk postulated a connection between this disease and a deficiency of some nutrients. A few years later, Goldberger et al. showed that pellagra can be prevented by adding fresh meat, eggs and milk to the diet. Subsequently, Goldberger created an excellent experimental model of pellagra (“black tongue”) by keeping dogs on an inadequate diet. Pellagra was initially thought to be caused by a deficiency of essential amino acids, but it was soon shown that the disease was prevented by one of the heat-stable factors present in water-soluble B vitamin preparations.
In 1935, Warburg et al. Nicotinic acid amide (nicotinamide) was obtained from a coenzyme isolated from horse erythrocytes. This has drawn attention to the role of niacin in nutrition. Since it was known that pellagra in humans and “black tongue” in dogs can be cured with liver extracts, in 1937 Elveheim, analyzing such extracts, discovered nicotinamide in them and showed that it was responsible for the therapeutic effect. Then it was found that synthetic derivatives of nicotinic acid have a similar effect. Even earlier, Goldberger and Tanner found that taking tryptophan helps with pellagra. It was later discovered that this was due to the conversion of tryptophan to nicotinic acid. A diet low in niacin and tryptophan caused pellagra in humans (Goldsmith, 1958).
In order not to confuse nicotinic acid with the alkaloid nicotine, it is sometimes also called niacin. Pellagra is now very rare in the United States, probably because niacin has been added to flour since 1939. Structure. In the body, nicotinic acid is converted into NAD or NADP. It is important to note that in both compounds, nicotinic acid is present in the form of nicotinamide. The structural formulas of NAD and NADP are shown below; the letter R in the structure of NAD denotes hydrogen (H), and in the structure of NADP the group P03H2. Analogues of nicotinic acid, which are its antagonists, have been synthesized: pyridine-3-sulfonic acid and 3-acetylpyridine.
Pharmacological action[edit | edit code]
Nicotinic acid and nicotinamide perform the same functions in the body. However, their pharmacological properties are not the same, since nicotinamide is not formed directly from nicotinic acid, but only from the breakdown of NAD. The toxic effect of nicotinic acid in humans (hot flashes, itching, dysfunction of the gastrointestinal tract and liver, exacerbation of peptic ulcer disease) usually appears only when using large doses (2-6 g/day), which are sometimes used to treat hyperlipoproteinemia (Chapter 36). Physiological functions. Biologically active forms of nicotinic acid, NAD and NADP, play a critical role in metabolism, being coenzymes in many redox reactions of tissue respiration. By binding to the corresponding dehydrogenases, these coenzymes act as oxidizing agents: they accept electrons and hydrogen from substrates and acquire a reduced form - NADH and NADPH. The latter, in turn, are oxidized by flavoproteins. NAD also serves as a donor of the ADP-ribosyl group in the reactions of its transfer to proteins.
Structural formulas of nicotinic acid, nicotinamide, NAD and NADP.
The process of converting niacin into NAD has been studied in various cells, including human red blood cells. It is shown below (reactions 63.3-63.5). NADP is formed from NAD in reaction 63.6. The biosynthesis of NAD from tryptophan is more complex. Through several enzymatic reactions, tryptophan is converted into quinolinic acid, and the latter into nicotinic acid ribonucleotide, which enters into reaction 63.4.
Nicotinic acid + 5-phosphoribosyl-1-pyrophosphate -> nicotinic acid ribonucleotide + pyrophosphate, (63.3)
nicotinic acid ribonucleotide + ATP -> desamido-NAD + pyrophosphate, (63.4)
desamido-NAD + glutamine + ATP —> NAD + glutamate + ADP + phosphate, (63.5)
NAD + ATP -> NADP + ADP. (63.6)
Deficiency symptoms[edit | edit code]
Nicotinic acid deficiency leads to the development of pellagra. Pellagra mainly affects the skin, gastrointestinal tract and central nervous system. The triad of symptoms - dermatitis, diarrhea and dementia - is often called the three D syndrome. Currently, pellagra is most often observed in alcoholism, protein-energy deficiency and deficiency of many vitamins. Initially, erythema, resembling a sunburn, appears on the back of the hands. Later, other exposed parts of the body (forehead, neck and legs) are affected. The damage can then spread more widely. Pellagra is characterized by symmetrical lesions of the skin, which sometimes darkens, flakes and becomes covered with scars.
Lesions of the gastrointestinal tract are manifested mainly by stomatitis, enteritis and diarrhea. The tongue becomes bright red, swells and sometimes ulcerates. Salivation increases and the salivary glands enlarge. Nausea and vomiting often occur. Sometimes, even in the absence of diarrhea, steatorrhea occurs. Diarrhea, if present, often recurs, and stools may be watery and even bloody.
Damage to the central nervous system is manifested by headache, dizziness, insomnia, depression and memory impairment. In severe cases, delusions, hallucinations, and dementia may occur. Conduction along motor and sensory nerves is disrupted. Laboratory testing usually reveals macrocytic anemia, hypoalbuminemia, and hyperuricemia.
They tried to judge the degree of nicotinic acid deficiency by the excretion of its methylated derivatives (in particular, N-methylnicotinamide) in the urine, but this indicator turned out to be unreliable, as was the level of nicotinamide in the blood or urine. The basis for diagnosis in most cases remains clinical manifestations in combination with the effect of exogenous nicotinamide.
Side effects
In addition to all its positive effects, niacin has some negative features: to large doses, over 50 mg taken orally and from 10 mg intramuscularly or intravenously, the body can react with hyperemia and hyperthermia of the skin in the arms, legs, knees, head, neck and chest. . This phenomenon is associated with the release of histamine. To dampen this reaction, you need to take a quick-acting antihistamine. As a rule, there is no need to take them, since hyperthermia from the moment of its development goes away completely within half an hour, a maximum of an hour.
Before using niacin, it is recommended to consult a specialist, since it may be contraindicated for people with hypotension or low blood viscosity.
Need[edit | edit code]
As noted above, the need for nicotinic acid can be satisfied not only by this acid itself, but also by nicotinamide, as well as tryptophan. Therefore, the need for nicotinic acid is influenced by the quantity and quality of protein in the diet. Based on urinary excretion of metabolites, 60 mg of tryptophan is on average equivalent to 1 mg of niacin. Oral contraceptives slow down the conversion of tryptophan to niacin. The minimum requirement for nicotinic acid (taking into account that formed from tryptophan) is on average 4.4 mg/1000 kcal. The daily requirement is 14 mg for women and 16 mg for men (Table XIII.2).
The dependence of the need for nicotinic acid on the amount of tryptophan in food explains the long-known connection between the prevalence of pellagra and the content of corn in the diet. Corn protein is low in tryptophan, and niacin is not readily available in corn and other grain products. If the bulk of dietary protein comes from grain products containing little tryptophan, then more niacin is needed to prevent pellagra. Americans consume a lot of animal protein, and therefore their daily requirement for niacin is largely covered by tryptophan.
Methods
The databases MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov and TrialResults-center (up to October 2017) were searched for studies.
The systematic review included clinical studies evaluating the use of the drug for the treatment of cardiovascular diseases. The meta-analysis included randomized clinical trials that assessed at least 1 long-term cardiovascular effect of niacin.
As primary endpoints
included cardiovascular disease, mortality from ischemic heart disease, as well as acute coronary syndrome, non-fatal and fatal stroke, revascularization and major adverse events.
Food sources[edit | edit code]
Sources of niacin include liver, meat, fish, poultry, nuts and beans, as well as bread and cereals, primarily enriched or coarsely ground. Animal protein is especially rich in tryptophan. Absorption, exchange and excretion. Both nicotinic acid and nicotinamide are easily absorbed in all parts of the intestine and enter all tissues. When therapeutic doses of nicotinic acid or nicotinamide are administered, only small amounts of these substances appear unchanged in the urine, whereas when very large doses are administered, both compounds are excreted in the urine largely unchanged. Nicotinic acid and nicotinamide are converted in the body mainly into N-methylnicotinamide, which undergoes further metabolic transformations. Application. Nicotinic acid, nicotinamide and their derivatives are used for the prevention and treatment of pellagra. Exacerbation of pellagra requires intensive treatment. It is recommended to take these drugs 50 mg orally up to ten times a day. If oral administration is not possible, the drug is administered 25 mg IV 2 times a day or more often. Symptoms of pellagra can appear with two types of metabolic disorders. In Hartnup's disease, tryptophan transport in the intestines and kidneys is impaired. In some cases of carcinoids, large amounts of tryptophan are consumed by tumor cells for the synthesis of 5-hydroxytryptophan and serotonin.
The effect of the introduction of nicotinic acid and its derivatives is observed very quickly. Within 24 hours, severe redness and swelling of the tongue disappear, and steatorrhea decreases. Lesions in the mouth and other mucous membranes heal quickly. Within 24 hours, nausea, vomiting and diarrhea may stop, and discomfort in the epigastrium disappears. abdominal pain and bloating. Appetite improves. Sometimes mental symptoms subside overnight. Confused consciousness clears up, patients calm down, begin to perceive their surroundings and become aware of their condition. Nicotinic acid and its derivatives have such a specific effect in this regard that they can be used as diagnostic agents for overt psychoses in the absence of other signs of pellagra. It is recommended to use large doses of nicotinic acid, especially when psychosis is combined with encephalopathy. Skin lesions, especially those that are weeping, hyperpigmented, and ulcerated, respond more slowly to treatment. The porphyrinuria characteristic of pellagra disappears.
Pellagra can be combined with vitamin B1 deficiency manifested by neuropathy. Vitamin B1 deficiency cannot be treated with nicotinic acid and its derivatives; in such cases, thiamine should be used. The condition of many patients with pellagra is also improved by additional administration of riboflavin and pyridoxine.
Nicotinic acid in gram doses reduces the concentrations of cholesterol and LDL triglycerides, fibrinogen and lipoprotein(a) in plasma. Therefore, it is used for hyperlipoproteinemia (Chapter 36).
Promising results have been obtained with the use of nicotinamide for the prevention of insulin-dependent diabetes mellitus in at-risk groups (Elliott et al., 1996; Lampeter et al., 1998). Extensive research into this problem is currently underway.
Publications in the media
Vitamin PP (vitamin B3, niacin, nicotinic acid, nicotinamide) is a water-soluble vitamin found in meat and fish products. Found in most foods containing vitamin B1. With severe food deficiency, pellagra develops. Endemic to some areas of Africa and Asia, sporadically found everywhere.
Sources of the vitamin are meat, liver, kidneys, milk, fish, yeast, vegetables, fruits, buckwheat.
Physiological role. Nicotinic acid amide is a prosthetic group that is part of NAD and NADP. NAD and NADP are hydrogen and electron acceptors and participate in redox processes, i.e. take part in cellular respiration.
Daily requirement • For adults — 18–24 mg • For children •• 6 months–1 year — 6 mg •• 1–1.5 years — 9 mg •• 1.5–2 years — 10 mg •• 3–4 years - 12 mg •• 5-6 years - 13 mg •• 7-10 years - 15 mg •• 11-13 years - 19 mg.
VITAMIN PP DEFICIENCY
Causes • Primary - lack of incoming food, for example, when corn predominates in the diet, since vitamin PP, although contained in it, is in a bound state and is not assimilated in the gastrointestinal tract. In addition, corn proteins are poor in tryptophan, which is used in the body for the synthesis of endogenous vitamin PP • Secondary - due to impaired absorption or assimilation of vitamin PP, as well as an increase in the need for it •• Prolonged diarrhea •• Liver diseases (most often cirrhosis leads to deficiency) • • Alcoholism •• Parenteral nutrition without sufficient replacement of vitamins •• Malignant carcinoid tumors (increases the need for tryptophan) •• Diabetes •• Hartnup's disease.
Clinical picture. Vitamin PP deficiency causes dysfunction of the skin, mucous membranes, gastrointestinal tract and central nervous system. Characterized by the presence of three Ds (dermatitis, diarrhea, dementia) and damage to the mucous membranes.
• Stage of prehypovitaminosis - nonspecific disorders (weakness, fatigue, loss of appetite, etc.).
• Stages of hypo- and vitamin deficiency •• Dermatitis. Skin lesions can be of four types. Most often it is symmetrical and occurs on areas of the skin exposed to solar radiation or trauma (pressure) ••• Skin manifestations in the form of pellagritic erythema occur acutely, followed by the formation of blisters, blisters, and crusts. A secondary infection is often associated ••• Damage to skin folds - redness, maceration, erosion and the addition of a secondary infection ••• Chronic hypertrophic changes - the skin thickens, loses elasticity, becomes folded. Marked pigmentation is noted in open areas of the body and in places subject to pressure. The lesions have a clear boundary and are surrounded by a border of recovering epithelium ••• Chronic atrophic changes in the skin with loss of elasticity and peeling. Characteristic of long-term forms of pellagra •• Damage to the mucous membranes primarily affects the oral cavity, although the mucous membranes of the vagina and urethra may be involved ••• Acute failure is characterized by glossitis and stomatitis, and the tongue becomes bright red in color. Initially, the tip and edges of the tongue are involved in the process, as well as areas of the mucous membrane surrounding the outlet of the Stenon's duct ••• Gradually the entire mucous membrane is involved, the tongue becomes painful and swollen, hypersalivation occurs ••• In the later stages of the disease, a characteristic picture of a lacquered tongue appears ( bright red tongue with a smooth surface due to atrophy of the papillae) ••• Ulcers may appear on the mucous membrane of the floor of the mouth, lower lip, and also opposite the molars •• Diarrhea is the most characteristic sign of dysfunction of the digestive system. Gastrointestinal tract involvement occurs in the later stages of the disease. Characterized by the appearance of a burning sensation in the mucous membrane of the oral cavity, pharynx, esophagus; gastric dyspepsia occurs in the form of nausea, less often vomiting, which is caused by atrophic changes in the gastric mucosa and the occurrence of achylia. Possible diarrhea alternating with constipation. A severe course is indicated by diarrhea streaked with blood as a result of the formation of erosions and ulcers of the intestinal mucosa •• Dementia is the most striking sign of damage to the central nervous system; may be accompanied by organic psychosis and/or encephalopathic syndrome. In the early stages, irritability appears, signs of polyneuritis are possible ••• Organic psychosis is manifested by hallucinatory-paranoid, affective symptoms, psychomotor agitation ••• Encephalopathic syndrome, characterized by blackouts, hypertonicity of the muscles of the limbs, the appearance of uncontrolled sucking and grasping reflexes •• In the later stages, they are impaired functions of the endocrine system, hypoproteinemia occurs.
Diagnosis • Urinary excretion of N'-methylnicotinamide less than 4 mg/day • Decreased nicotinic acid levels • Decreased levels of other B vitamins in the blood and urine.
Differential diagnosis - other causes of stomatitis, glossitis, diarrhea, dementia. When signs of central nervous system disorders appear, it is necessary to differentiate from those with vitamin B1 deficiency.
Treatment • In moderate and severe cases, hospitalization is necessary • Diet. Inclusion in the diet of foods rich in vitamin PP (meat, eggs) and tryptophan (milk) • Prescription of nicotinic acid (or nicotinamide) from 300 to 1000 mg/day orally at the beginning of treatment with a marked decrease in the content of vitamin PP in the blood plasma, then 300 –500 mg • For gastrointestinal diseases, nicotinic acid (or nicotinamide) is administered parenterally (50–100 mg IM 2–5 times a day or 25–100 mg IV) • At the same time, 5 mg of thiamine, riboflavin and pyridoxine are prescribed • Caution should be exercised when using nicotinic acid with concomitant glaucoma (possible exacerbation), gout (large doses cause hyperuricemia), liver pathology (large doses can have a hepatotoxic effect), arterial hypotension (due to the vasodilator effect of the drug), peptic ulcer (possible exacerbation ) • To reduce the side effects of nicotinic acid (redness of the face and upper half of the body, dizziness, rash), it is recommended to start treatment with low doses of the drug and gradually increase them, and/or take nicotinic acid orally after meals or with milk. Tolerance to the vasodilatory effect of nicotinic acid usually develops within the first 2 weeks • Nicotinamide, unlike nicotinic acid, does not have a vasodilatory effect.
The course is usually progressive.
Prevention • Nutrition with sufficient dietary content of foods rich in nicotinic acid • In the endogenous form - timely diagnosis and treatment of diseases that impair the absorption and assimilation of vitamin PP, prophylactic administration of nicotinic acid preparations; additional administration of vitamin PP to persons with an increased need for it.
Synonyms • Asturian rose disease • Rose disease • Pellagra • Lombardy pellagra • Scorbutum alpine
ICD-10 • E52 Nicotinic acid deficiency [pellagra]
