Nicotinic Acid: Definition, Dietary Recommendations, Medical Uses, History, Contraindications and Side Effects

Also known as niacin, it is an organic compound and according to the definition used, it is one of the 20 to 80 essential human nutrients.

Along with nicotinamide forms the group known as vitamin B3 complex. It has the formula C6H5NO2 and belongs to the group of pyridinecarboxylic acids.

Medications and supplemental niacin are used primarily to treat high blood cholesterol and pellagra (niacin deficiency). An insufficient amount of niacin in the diet can cause nausea, skin and mouth lesions, anemia, headaches and fatigue.

The lack of niacin can also be observed in pandemic disease, which is caused by the lack of five essential vitamins (niacin, vitamin C, thiamin, vitamin D, and vitamin A) and is generally found in areas of widespread poverty and malnutrition. .

Niacin is provided in the diet from a variety of whole and processed foods, with the highest content in fortified packed foods, tuna, some vegetables and other animal sources. Some countries require their addition to grains.

This colorless solid, soluble in water, is a derivative of pyridine, with a carboxyl group in the 3-position.

Other forms of vitamin B3 include the corresponding nicotinamide amide (niacinamide), where the carboxyl group has been replaced by a carboxamide group, as well as more complex amides and a variety of esters.

Nicotinic acid and niacinamide are convertible to each other with a constant global demand that increases from 8,500 tons per year in the 1980s to 40,000 tons in recent years.

Niacin can not be directly converted to nicotinamide, but both compounds are precursors of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate in vivo.

Nicotinamide adenine dinucleotide is converted to nicotinamide adenine dinucleotide phosphate by phosphorylation in the presence of the enzyme NAD + kinase.

Nicotinamide adenine dinucleotide phosphate and nicotinamide adenine dinucleotide are coenzymes for many dehydrogenases, which participate in many processes of hydrogen transfer.

Nicotinamide adenine dinucleotide is important in the catabolism of fats, carbohydrates, proteins and alcohol, as well as cell signaling and DNA repair, and nicotinamide adenine dinucleotide phosphate mainly in anabolic reactions such as fatty acids and cholesterol synthesis.

The requirements of high energy (brain) or high turnover rate (intestine, skin) are usually the most susceptible to its deficiency.

Supplementation with niacin has not been found useful to reduce the risk of cardiovascular disease, but it seems to be effective in those who do not take statins.

Although niacin and nicotinamide 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 redness. As a precursor to nicotinamide adenine dinucleotide and adenine dinucleotide phosphate, niacin is also involved in DNA repair.

Dietary recommendations

The US Institute of Medicine UU updated the estimated average requirements and recommended diets for B vitamins in 1998.

Current Estimated Average Requirements for niacin for women and men 14 years and older are 11mg / day and 12mg / day, respectively; The recommended dietary diets are 14 and 16mg / day, respectively.

The recommended dietary allowances are higher than the estimated average requirements in order to identify amounts that will cover people with above-average requirements.

The recommended dietary intake for pregnancy is 18mg / day. The recommended dietary allowance for breastfeeding is 17 mg / day. For babies up to 12 months, the adequate intake (AI) is 2-4mg / day.

For children from 1 to 13 years, the recommended daily amount increases with the age of 6 to 12 mg / day. Regarding safety, the Institute of Medicine establishes tolerable levels of maximum intake of vitamins and minerals when the evidence is sufficient.

In the case of niacin, the upper intake level is set at 35mg / day. Taken together, the estimated average requirements, recommended diets, AIs, and higher intake levels are called dietary reference intakes.

The European Food Safety Authority refers to the collective set of information as dietary reference values, with reference intake of population instead of recommended dietary allowance, and the average requirement instead of the estimated average requirement.

Adequate intake and upper intake level are defined in the same way as in the United States. For women (including pregnant or lactating women), men and children, the reference intake of the population is 1.6 mg of niacin per megajoule (MJ) of energy consumed.

Since the conversion is 1 MJ = 238.8 kcal, an adult who consumes 2388 calories should consume 16 mg of niacin. This is comparable to the recommended US diets. UU The maximum level of niacin intake is set at 10mg / day, which is much lower than the value of the US. UU

The upper intake level is applied to niacin as a supplement that is consumed as a dose, and with the intention of avoiding the reaction of redness of the skin. This explains why the population reference intake may be higher than the higher intake level.

Both the dietary reference intake and the dietary reference values ​​describe the amounts needed as niacin equivalents, calculated as 1 mg of niacin equivalents = 1 mg of niacin or 60 mg of the essential amino acid tryptophan.

This is because the amino acid is used to synthesize the vitamin.

For US labeling of food and dietary supplements. UU., The amount in a portion is expressed as a percentage of the daily value (% DV).

For niacin labeling purposes, 100% of the daily value was 20mg, but as of May 27, 2016 it was modified to 16mg in order to agree with the recommended dietary allowance.

A table of the daily values ​​of old and new adults in the daily reference intake is provided.

The original deadline to comply was July 28, 2018, but on September 29, 2017, the food and drug administration published a proposed rule that extended the deadline until January 1, 2020 for large companies and on January 1. of 2021 for small businesses.

Food sources

Niacin is found in a variety of whole and processed foods, including fortified packed foods, meat from various animal sources, seafood and spices.

Among the sources of whole foods with the highest niacin content per 100 grams:

  • Cooked tuna, 18.8 mg.
  • Turkey cooked in light meat, 11.8 mg.
  • Cooked lean pork, 11.1 mg.
  • Cooked venison, 10.8 mg.
  • Lean cooked beef, 8.0 mg.
Plant foods and spices
  • Sesame seed flour, 12.5 mg.
  • Ground ginger, 9.6 mg.
  • Dry tarragon, 9.0 mg.
  • Dry green peppers, 7.4 mg.
  • Portabella mushrooms on the grill, 6.2 mg.
  • Roasted sunflower seeds, 4.1 mg.
  • Dehydrated apricots, 3.6 mg.
  • Baked potato, 3.1 mg.

Fortified breakfast cereals have one of the highest contents of niacin (more than 20 mg per 100 grams). Whole wheat flours, such as wheat, rice, barley or corn, and pasta have niacin contents in a range of 3mg – 10mg per 100 grams.

Medical uses

Abnormal lipids

Niacin has sometimes been used in addition to other lipid-lowering medications. The systematic reviews found no effect of niacin on cardiovascular disease or death, despite elevating high-density lipoprotein cholesterol and reported side effects, including an increased risk of diabetes.

Deficiency treatment

Niacin and niacinamide are used for the prevention and treatment of pellagra.


Niacin is contraindicated with active liver disease, persistent elevated serum transaminases, active peptic ulcer disease, or arterial hemorrhage.

Side effects

The most common side effects are flushing (for example, heat, itching or tingling), headache, general pain, abdominal pain, diarrhea, dyspepsia , nausea, vomiting, rhinitis , pruritus and rash.

These can be minimized by starting therapy at low doses, gradually increasing the dose and avoiding administration on an empty stomach. High doses of niacin often temporarily reduce blood pressure as a result of acute vasodilation.

In the longer term, the use of high doses of niacin can persistently reduce blood pressure in individuals with hypertension , but more research is needed to determine the extent of this effect.

Redness of the face

The redness usually lasts 15 to 30 minutes, although sometimes it can last up to two hours. Sometimes it is accompanied by a sensation of itching or itching, particularly in areas covered by clothing.

Redness can be blocked by taking 300mg of aspirin half an hour before taking niacin, taking one tablet of ibuprofen per day or co-administering the prostaglandin receptor antagonist laropiprant.

Taking niacin with meals also helps reduce this side effect. Acquired tolerance will also help reduce redness. After several weeks of a constant dose, most patients no longer experience redness.

The reduction of redness focuses on altering or blocking the pathway mediated by prostaglandins. Slow-release or “sustained” forms of niacin have been developed to decrease these side effects.

One study showed that the incidence of redness was significantly lower with a sustained-release formulation, although doses greater than 2gm per day have been associated with liver damage, particularly with slow-release formulations.

Prostaglandin (PGD2) is the main cause of the redness reaction, and serotonin seems to play a secondary role in this reaction. The effect is mediated by prostaglandin E2 and D2 due to the activation of GPR109A of epidermal Langerhans cells and keratinocytes.

Langerhans cells use cyclooxygenase type 1 (COX-1) for the production of PGE2 and are more responsible for acute irrigation, while keratinocytes are dependent on COX-2 and are in an active continuous vasodilation.

It was thought that the redness involved histamine , but it has been shown that histamine is not involved in the reaction.

Gastrointestinal and hepatic

Gastrointestinal complaints have also been reported, such as indigestion, nausea and liver failure. Hepatotoxicity is possibly related to metabolism through amidation resulting in the production of nicotinamide adenine dinucleotide.

The release form over time has a lower therapeutic index to lower serum lipids relative to this form of toxicity.


It has been shown that the high doses of niacin used to improve the lipid profile raise blood sugar by 5% – 10%, thus worsening diabetes mellitus. Niacin therapy increases the risk of new onset diabetes by approximately 34%.

The hyperuricemia is another side effect of high doses of niacin and can exacerbate gout.


Side effects of cardiac arrhythmias have also been reported. An increase in prothrombin time and a decrease in platelet count have been reported; therefore, these should be closely monitored in patients who are also taking anticoagulants.

In particular, the extended-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 the retina, which leads to blurred vision and blindness. This maculopathy is reversible after the niacin intake stops.

The pregnancy

Niacin in doses used to reduce cholesterol levels has been associated with birth defects in laboratory animals, with possible consequences for the development of children in pregnant women.


Between 1906 and 1940, more than 3 million Americans were affected by pellagra with more than 100,000 deaths. Joseph Goldberger was assigned to study pellagra by the surgeon general of the United States and produced good results.

At the end of the 1930s, studies by Tom Spies , Marion Blankenhorn and Clark Cooperestablished that niacin cured pellagra in humans. The disease was greatly reduced as a result.

Currently, niacin deficiency is sometimes seen in developed countries, and is generally evident in conditions of poverty, malnutrition and chronic alcoholism.

It also tends to occur in less developed areas where people eat corn as a staple food, since corn is the only grain with a low digestible niacin content.

A cooking technique called nixtamalization, that is, pretreatment with alkaline ingredients, increases the bioavailability of niacin during the production of corn flour.

For this reason, people who consume corn as tortillas are not at risk for niacin deficiency.

It has been shown that mild deficiency of niacin decreases metabolism, which causes a decrease in cold tolerance.

Severe niacin deficiency in the diet causes pellagra disease, which is characterized by diarrhea, dermatitis and dementia, as well as Casal collar injuries in the lower neck, hyperpigmentation, thickening of the skin, inflammation of the mouth and the tongue, digestive disorders, amnesia, delirium and eventually death, if not treated.

The common psychiatric symptoms of niacin deficiency include irritability, lack of concentration, anxiety, fatigue, restlessness, apathy and depression .

Studies have indicated that, in patients with alcoholic pellagra, niacin deficiency can be an important factor that influences both the onset and severity of this condition.

Patients with alcoholism generally experience greater intestinal permeability, which leads to negative health outcomes.

Hartnup’s disease is a hereditary nutritional disorder that produces 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, which makes it difficult for the body to decompose and absorb tryptophan in the diet (an essential amino acid used to synthesize niacin).

The resulting condition is similar to pellagra, including the symptoms of red, scaly rash and sensitivity to sunlight.

Oral niacin is given as a treatment for this condition in doses ranging from 40mg to 200mg, with a good prognosis if they are identified and treated early.

The synthesis of niacin is also deficient in the carcinoid syndrome, due to the metabolic deviation of its precursor tryptophan to form serotonin.



The therapeutic effects of niacin are mediated in part by the activation of G-protein coupled receptors, including niacin receptor 1 (NIACR1) and niacin receptor 2 (NIACR2) that are expressed in adipose tissue, spleen, immune cells and keratinocytes but not in other expected organs such as liver, kidney, heart or intestine.

The niacin receptor 1 (NIACR1) and niacin receptor 2 (NIACR2) inhibit the production of cyclic adenosine monophosphate and therefore the breakdown of fat in adipose tissue and free fatty acids available for liver to produce triglycerides and very low density lipoproteins and in Low-density lipoprotein or “bad” cholesterol.

The decrease in free fatty acids also suppresses the hepatic expression of apolipoprotein C3 (APOC3) and coactivator-1b of PPARg (PGC-1b), which increases very low density lipoproteins and reduces their production. It also inhibits diacylglycerol acyltransferase-2 (important synthesis of hepatic TG).

The mechanism behind the increase in high-density lipoprotein cholesterol is not fully understood, but it seems to be done in several ways. Niacin increases the levels of apolipoprotein A1 due to the anticatabolic effects that result in increased transport of reverse cholesterol.

It also inhibits the hepatic absorption of high density lipoprotein cholesterol, producing down-regulation of the cholesterol ester transfer protein gene.

Finally, it stimulates the ABCA1 transporter in monocytes and macrophages and upregulates the receptor activated by the peroxisome proliferator and results in the transport of reverse cholesterol.

Reduces secondary outcomes associated with atherosclerosis, such as low density lipoprotein cholesterol, very low density lipoprotein cholesterol and triglycerides (TG), but increases high density lipoprotein cholesterol.

Despite the importance of other cardiovascular risk factors, high density lipoprotein cholesterol was associated with fewer cardiovascular events, regardless of the reduction in low density lipoproteins.

Other effects include antithrombotic and vascular inflammation, improved endothelial function and plaque stability.

Niacin also appears to upregulate the neurotrophic factor derived from the brain and the expression of kinase B of the tropomyosin receptor.

The research has been able to show the role of niacin in the lipid metabolism of the route.

It is observed that this vitamin can decrease the synthesis of apoB-containing lipoproteins, such as very low density lipoproteins, low density lipoproteins, intermediate density lipoproteins and lipoproteins through several mechanisms:

Direct inhibition of the action of DGAT2, a key enzyme for triglyceride synthesis, has the ability to bind to the HCAR2 receptor, thus decreasing lipolysis and the flow of free fatty acid to the liver for triglyceride synthesis and increased apoB catabolism.

On the other hand, niacin increases cholesterol levels of high density lipoproteins through direct and indirect pathways.

Niacin decreases the mass and activity of cholesterol ester transfer protein, and this synergistic effect with decreasing triglyceride levels can indirectly raise cholesterol levels of high density lipoproteins.

The study has also been able to show direct effects on the beta chain of ATP synthase and on the production and hepatic uptake of apoA-I also increases cholesterol levels of high density lipoproteins.

Therefore, by affecting the pathway, reducing lipid levels helps reduce cardiovascular disease.


The liver can synthesize niacin from the essential amino acid tryptophan, which requires 60 mg of tryptophan to produce 1 mg of niacin. Riboflavin, vitamin B6 and iron are necessary in some of the reactions involved in the conversion of tryptophan to nicotinamide adenine dinucleotide.

Physical and chemical properties

Laboratory synthesis

Several thousand tons of niacin are manufactured each year, from 3-methylpyridine.


Niacin is available as a prescription product, and in the United States as a dietary supplement. The prescription products can be immediate release (Niacor, 500mg tablets) or extended-release (Niaspan tablets, 500mg and 1000mg).

Dietary supplement products can be immediate or slow release, the latter includes inositol hexanicotinate.

Over-the-counter niacin is not federally regulated in the United States. Some “no-flush” types, such as inositol hexanicotinate, contain convertible niacin compounds, but have little clinical efficacy in reducing cholesterol levels.

Prolonged release

A prescription extended-release niacin, Niaspan, has a film coating that delays the release of niacin, resulting in absorption over a period of 8-12 hours.

Prolonged-release formulations generally reduce the side effects of vasodilation and redness, but increase the risk of hepatotoxicity compared to 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 that has been shown to reduce vasodilation and redness by up to 73%.

The HPS2-THRIVE study, a study sponsored by Merck, showed no additional efficacy for Tredaptive to lower cholesterol when used in combination with other statin drugs, but showed an increase in other side effects.

The study resulted in the complete withdrawal of Tredaptive from the international market.

Hexanicotinate of inositol

One form of dietary supplement is inositol hexanicotinate, which is inositol that has been esterified with niacin in the six alcohol groups of inositol.

Inositol hexanicotinate is generally sold as “rinse-free” or “rinse-free” niacin in units of 250, 500 or 1000 mg / tablets or capsules.

It is sold as an over-the-counter formulation, and is often marketed and labeled as niacin, which misleads consumers into thinking they are receiving the active form of the drug.

While this form of niacin does not cause the redness associated with immediate release products, the evidence that it has lipid modifying functions is disputed.

As clinical trials date from the early 1960s (Dorner, Wales) or the late 1970s (Ziliotto, Kruse, Agusti), it is difficult to evaluate them according to current standards.

One of the latest studies confirmed the superiority of inositol and xanthinol esters of nicotinic acid to reduce free fatty acids in serum, but other studies conducted during the same period found no benefit.

The studies explain that this is mainly due to the fact that preparations “without irrigation” do not contain any free nicotinic acid.

A more recent placebo-controlled trial was small (n = 11 / group), but results after three months at 1500mg / day did not show a trend for improvements in total cholesterol, low-density lipoprotein cholesterol, high lipoprotein cholesterol density or triglycerides.

Therefore, until now there is not enough evidence to recommend inositol hexanicotinate to treat dyslipidemia.


Nicotinamide can be obtained from the diet in which it is present mainly as nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

These are hydrolysed in the intestine and the resulting nicotinamide is absorbed as such or after its hydrolysis to nicotinic acid.

Nicotinamide is present in nature only in small amounts. In non-prepared foods, niacin is present mainly in the form of the nucleotides of cellular pyridine nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

Enzymatic hydrolysis of coenzymes can occur during the course of food preparation. Boiling releases most of the total niacin present in sweet corn such as nicotinamide (up to 55 mg / kg).

Nicotinamide can be toxic to the liver at doses higher than 3 g / day for adults.


Niacin was first described by the chemist Hugo Weidel in 1873 in his studies on nicotine. The original preparation is still useful: the oxidation of nicotine with nitric acid.

For the first time, niacin was extracted by Casimir Funk, but he thought it was thiamine and due to the group of amine discovered he coined the term “vitamin”.

Niacin was extracted from the livers by the biochemist Conrad Elvehjem in 1937, who later identified the active ingredient, then known as the “pellagra prevention factor” and the “factor against the black tongue”.

Shortly thereafter, in studies conducted in Alabama and Cincinnati, Dr. Tom Spies discovered that nicotinic acid cured those who suffered from pellagra.

Niacin is known as vitamin B3 because it was the third of the B vitamins that was discovered. Historically it has been called “vitamin PP”, “vitamin PP” and “factor PP”, which is derived from the term “preventive factor of pellagra”.

When the biological importance of nicotinic acid was realized, it was considered appropriate to choose a name to dissociate it 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. Carpenter discovered in 1951 that niacin in corn is not biologically available and that it can be released only in very alkaline lime water at pH 11.

In 1955, Altschul and his colleagues described that niacin has a property to reduce lipids. As such, niacin is the oldest lipid-lowering drug.


In animal and in vitro models, niacin produces marked anti-inflammatory effects in a variety of tissues, including the brain, gastrointestinal tract, skin and vascular tissue, through activation of the niacin receptor 1 (NIACR1).

Niacin has been shown to attenuate neuroinflammation and may be effective in the treatment of neuroimmune disorders such as multiple sclerosis and Parkinson’s disease.

Unlike niacin, nicotinamide does not activate the niacin 1 receptor (NIACR1), however, both niacin and nicotinamide activate the G protein-coupled estrogen receptor (GPER) in vitro.