Niacin, also known as nicotinic acid or vitamin B3, is a type of B vitamin. It is water-soluble, which means it dissolve in water, and therefore is not stored in the body. Its derivatives such as NADH, NAD, NAD+, and NADP play essential roles in energy metabolism in the living cell and DNA repair. The designation vitamin B3 also includes the corresponding amide nicotinamide (or “niacinamide”), whose chemical formula is C6H6NO2. Niacin also assists in the functioning of the digestive system, skin, and nerves, among many other functios. Leftover amounts of the vitamin leave the body through the urine. That means you need a continuous supply of such vitamins in your diet.

Synonyms

3-Pyridine carboxamide, anti-blacktongue factor, antipellagra factor, B-complex vitamin, benicot, Efacin®, ENDUR-ACIN®, Enduramide®, Hexopal®, NIAC®, Niacor®, Niaspan®, Nicalex®, nicamid, Nicamin®, Nico-400®, Nicobid®, Nicolar®, Nicotinex®, nicosedine, Nico-Span®, nicotinamide, nicotinic acid amide, nicotinic amide, nicotylamidum, Papulex®, pellagra preventing factor, Slo-Niacin®, Tega-Span®, Tri-B3®, Wampocap®.

A bit of History

Niacin was first discovered from the oxidation of nicotine to form nicotinic acid. When the properties of nicotinic acid were discovered, it was thought prudent to choose a name to dissociate it from nicotine, in order to avoid the perception that vitamins or niacin-rich food contain nicotine. The resulting name ‘niacin’ was derived from nicotinic acid + vitamin.

Niacin is also 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”, a name derived from the term “pellagra-preventing factor”, because the disease pellagra, characterized by cracked, scaly, discolored skin, digestive problems, and overall bodily weakness, is due to a deficiency of niacin in the diet.

Early records of pellagra followed the widespread cultivation of corn in Europe in the 1700’s. The disease was generally associated with poorer social classes whose chief dietary staple consisted of cereals like corn or sorghum. Pellagra was also common in the southern United States during the early 1900’s where income was low and corn products were a major dietary staple. Interestingly, pellagra was not known in Mexico, where corn was also an important dietary staple and much of the population was also poor. In fact, corn contains appreciable amounts of niacin, but it is present in a bound form that is not nutritionally available to humans. The traditional preparation of corn tortillas in Mexico involves soaking the corn in a lime (calcium oxide) solution, prior to cooking. Heating the corn in an alkaline solution releases the tryptophan (a niacin precursor) from the corn in a process called nixtamalization so that it can be absorbed in the intestine, and converted to niacin.

Biochemical Functions

Redox (oxidation-reduction) Reactions

Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. As many as 200 enzymes require the niacin coenzymes, NAD and NADP (its derivatives), mainly to accept or donate electrons for redox reactions. NAD functions most often in energy producing reactions involving the degradation (catabolism) of carbohydrates, fats, proteins, and alcohol. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of all macromolecules, including fatty acids and cholesterol.

Non-redox reactions

The niacin coenzyme, NAD, is the substrate (reactant) for two classes of enzymes (mono-ADP-ribosyltransferases and poly-ADP-ribose polymerase) that separate the niacin moiety from NAD and transfer ADP-ribose to proteins. Mono-ADP-ribosyltransferase enzymes were first discovered in certain bacteria, where they were found to produce toxins, such as cholera and diptheria. These enzymes and their products, ADP-ribosylated proteins, have also been found in the cells of mammals and are thought to play a role in cell signaling by affecting G-protein activity. G-proteins are proteins that bind guanosine-5′-triphosphate (GTP) and act as intermediaries in a number of cell-signaling pathways. Poly-ADP-ribose polymerases (PARPs) are enzymes that catalyze the transfer of many ADP-ribose units from NAD to acceptor proteins. PARPs appear to function in DNA repair and stress responses, cell signaling, transcription, regulation or apoptosis, chromatin structure, and cell differentiation, suggesting a possible role for NAD in cancer prevention. At least five different PARPs have been identified, and although their functions are not yet well understood, their existence indicates a potential for considerable consumption of NAD. A third class of enzymes (ADP-ribosyl cyclase) catalyzes the formation of cyclic ADP-ribose, a molecule that works within cells to provoke the release of calcium ions from internal storage sites and probably also plays a role in cell signaling.

With this in mind, we can understand how Niacin is responsable of the following functions:

Energy Production

Like its fellow B-complex vitamins, niacin is important in energy production. NAD and NADP are essential for conversion of the body’s proteins, fats, and carbohydrates into usable energy. Niacin is also used to synthesize starch that can be stored in the body’s muscles and liver for eventual use as an energy source.

Metabolism of Fats

Vitamin B3 plays a critical role in the chemical processing of fats in the body. The fatty acid building blocks for fat-containing structures in the body (like cell membranes) typically require the presence of vitamin B3 for their synthesis, as do many fat-based hormones (called steroid hormones).

Interestingly, although niacin is required for production of cholesterol by the liver, the vitamin has repeatedly been used to successfully lower total blood cholesterol in individuals with elevated cholesterol levels. This cholesterol-lowering effect of vitamin B3 only occurs at high doses that must be obtained through nutrient supplementation, and most likely involves a chemical feature of vitamin B3 that is not directly related to fat or fat processing.

Support of genetic processes

Components of the primary genetic material in our cells, called deoxyribose nucleic acid (DNA) require vitamin B3 for their production, and deficiency of vitamin B3 (like deficiency of other B-complex vitamins) has been directly linked to genetic (DNA) damage. The relationship between vitamin B3 and DNA damage appears to be particularly important in relationship to cancer and its prevention.

Regulation of insulin activity

Although experts cannot agree on the precise mechanism though which vitamin B3 affects blood sugar regulation and function of the hormone insulin, the vitamin has repeatedly been shown to be involved in insulin metabolism and blood sugar regulation. Some (but by no means all) researchers support the idea of a “glucose tolerance factor” (GTF) molecule that includes vitamin B3 and must be present for optimal insulin activity.

What are the consecuenses of vitamin B3 deficiency?

The most common symptoms of niacin deficiency involve the skin, digestive system, and the nervous system. The symptoms of pellagra were commonly referred to as the four D’s: dermatitis, diarrhea, dementia, and death. In the skin, a thick, scaly, darkly pigmented rash develops symmetrically in areas exposed to sunlight. In fact, the word “pellagra” comes from the Italian phrase for rough or raw skin. Symptoms related to the digestive system include a bright red tongue, vomiting, and diarrhea. Neurologic symptoms include headache, apathy, fatigue, depression, disorientation, and memory loss. If untreated, pellagra is ultimately fatal.

How do other nutrients interact with vitamin B3?

As described above, part of the body’s B3 supply comes from conversion of the amino acid tryptophan. Tryptophan deficiency can therefore increase risk of vitamin B3 deficiency. (Tryptophan deficiency is likely to occur in any individual with poor overall protein intake.) The conversion of tryptophan to vitamin B3 also requires the presence of vitamins B1 and B6, and when B1 and/or B6 are deficient, B3 can also become deficient.

Vitamin B3 deficiency also appears to be related to vitamin B12 status, since even mild deficiencies in vitamin B12 can increase loss of vitamin B3 in the urine.

Recommended Intake

Recommended daily allowances (RDAs) are defined as the levels of intake of essential nutrients that the Food and Nutrition Board at the Institute of Medicine has found to be adequate to meet the known nutrient needs of most healthy persons.

Specific recommendations for each vitamin depend on age, gender, and other factors (such as pregnancy). The general recommended intakes for niacin are listed below:

Infants

  • 0-6 months: 2 milligrams per day (mg/d)
  • 7-12 months: 4 mg/d

Children

  • 1-3 years: 6 mg/d
  • 4-8 years: 8 mg/d
  • 9-13 years: 12 mg/d

Adolescents and Adults

  • Age 14 and up: 14 to 16 mg/d
  • Pregnant women: 18 mg/d
  • Breastfeeding women: 17 mg/d

The RDA for niacin, revised in 1998, was based on the prevention of deficiency. Pellagra can be prevented by about 11 mg NE/day, but 12 mg to 16 mg/day has been found to normalize the urinary excretion of niacin metabolites (breakdown products) in healthy young adults.

The best way to get the daily requirement of essential vitamins is to eat a balanced diet that contains a variety of foods from the food guide pyramid

Food sources

Good sources of niacin include yeast, meat, poultry, red fishes (e.g., tuna, salmon), cereals (especially fortified cereals), legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin

How do cooking, storage, or processing affect vitamin B3?

Vitamin B3 is one of the more stable water-soluble vitamins and is minimally susceptible to damage by air, light, and heat.

Pharmacological uses

Niacin RDA can be easily achieved by diet, and therefore you wouldn´t need to seek another supplementation, but it was discovered that high doses of vitamin B3 had a very important role in the prevention and treatment of various diseases.

High cholesterol treatment

Niacin, not niacinamide in this case, is a well-accepted treatment for high cholesterol. Multiple studies show that niacin (not niacinamide) has significant benefits on levels of high-density cholesterol (HDL or “good cholesterol”), with better results than prescription drugs such as “statins” like atorvastatin (Lipitor®). There are also benefits on levels of low-density cholesterol (LDL or “bad cholesterol”), although these effects are less dramatic. Adding niacin to a second drug such as a statin may increase the effects on low-density lipoproteins. The use of niacin for the treatment of dyslipidemia associated with type 2 diabetes has been controversial because of the possibility of worsening glycemic control. Patients should check with a physician and pharmacist before starting niacin.

Pellagra

Niacin (vitamin B3) and niacinamide are FDA approved for the treatment of niacin deficiency, wich leads to Pellagra.

Atherosclerosis

Niacin decreases blood levels of cholesterol and lipoprotein (a), which may reduce the risk of atherosclerosis (“hardening” of the arteries). However, niacin also can increase homocysteine levels, which may have the opposite effect. Overall, the scientific evidence supports the use of niacin in combination with other drugs (but not alone) to decrease cholesterol and slow the process of atherosclerosis. More research is needed in this area before a firm conclusion can be drawn.

Alzheimer’s disease/ cognitive decline

Dementia can be caused by severe niacin insufficiency, but it is unclear whether variation in intake of niacin in the usual diet is linked to neurodegenerative decline or Alzheimer’s disease (AD). Further research is needed before a conclusion can be drawn.

Osteoarthritis

Preliminary human studies suggest that niacinamide may be useful in the treatment of osteoarthritis. Further research is needed before a recommendation can be made.

Toxicity

People taking pharmacological doses of niacin (1.5 – 6 g per day) often experience a syndrome of side-effects that can include one or more of the following:

  • dermatological complaints: facial flushing and itching, dry skin, skin rashes including acanthosis nigricans
  • gastrointestinal complaints: dyspepsia (indigestion)
  • liver toxicity: fulminant hepatic failure
  • hyperglycemia
  • cardiac arrhythmias
  • birth defects

Facial flushing is the most commonly reported side effect. It lasts for about 15-30 minutes, and is sometimes accompanied by a prickly or itching sensation. This effect is mediated by prostaglandins and can be blocked by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of ibuprofen per day. Taking the niacin with meals also helps reduce this side effect. After 1 to 2 weeks of a stable dose, most patients no longer flush. Slow or “sustained” release forms of niacin have therefore been developed to lessen these side effects. One study showed the incidence of flushing was 4.5x lower (1.9 vs. 8.6 episodes in the first month) with a sustained-release formulation.

Doses above 2 g per day have been associated with liver damage, particularly with slow-release formulations.

High-dose niacin may also elevate blood sugar, thereby worsening diabetes mellitus. Hyperuricemia is another side effect of taking high-dose niacin; thus niacin may worsen gout.

Niacin at doses used in lowering cholesterol has been associated with birth defects in laboratory animals and should not be taken by pregnant women.

Niacin at extremely high doses can have life-threatening acute toxic reactions. One patient suffered vomiting after taking eleven 500-milligram niacin tablets over 36 hours, and another was unresponsive for several minutes after taking five 500-milligram tablets over two days. Extremely high doses of niacin can also cause niacin maculopathy, a thickening of the macula and retina which leads to blurred vision and blindness.

Pregnancy and Breastfeeding

Use of niacin supplementation during pregnancy or breastfeeding is not recommended due to lack of sufficient research of safety and effectiveness.

Sources: Linus Pauling Institute, Wikipedia, Mayo Clinic, World´s healthiest foods

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