A water soluble B complex vitamin (B3).
Niacin, also known as vitamin B3, is one of the water-soluble B vitamins.
Generic name is nicotinic acid.
Niacin is naturally present in many foods, added to some food products, and available as a dietary supplement.
It is found in fortified flour and cereal.
Niacin is available in multivitamin products, in supplements containing other B-complex vitamins, and in supplements containing niacin only.
Nicotinic acid and nicotinamide are the two most common forms of niacin in supplements.
Some niacin-only supplements contain 500 mg or more per serving, which is much higher than the recommended daily allowance.
Most dietary niacin is in the form of nicotinic acid and nicotinamide.
Some foods contain small amounts of NAD and NADP.
Tryptophan an amino acinar protein is converted in the body to NAD, so it is considered a dietary source of niacin.
People who do not consume enough riboflavin, pyridoxine (vitamin B6), or iron convert less tryptophan to niacin because enzymes in the metabolic pathway for this conversion depend on these nutrients to function.
People with ((Hartnup disease)): rare genetic disorder involving the renal, intestinal, and cellular transport processes for several amino acids, including tryptophan.
Hartnup disease interferes with the absorption of tryptophan in the small intestine and increases its loss in the urine via the kidneys: resulting , the body having less available tryptophan to convert to niacin.
In Carcinoid syndrome tryptophan is preferentially oxidized to serotonin and not metabolized to niacin.
The body has less available tryptophan to convert to niacin.
NAD and NADP consumed in foods are converted to nicotinamide in the gut and then absorbed.
Niacin is present in a wide variety of foods: including poultry, beef, and fish providing about 5-10 mg niacin per serving, primarily in the highly bioavailable forms of NAD and NADP
Plant-based foods, such as nuts, legumes, and grains, provide about 2-5 mg niacin per serving, mainly as nicotinic acid.
In some grain products, niacin is highly bound to polysaccharides and glycopeptides that make it only about 30% bioavailable.
Many breads, cereals, and infant formulas contain added niacin in its free form and therefore highly bioavailable.
Foods with the amino acid tryptophan are sources of niacin as they can be converted to NAD, mainly in the liver.
Foods with niacin includes a variety of vegetables; fruits; grains; fat-free and low-fat milk, yogurt, and cheese; and oils.
Enriched grains are also a source of niacin.
Protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.
Fish, beef, chicken, and turkey are good sources of niacin.
Many legumes, nuts, seeds, and soy products provide some niacin.
The estimate of efficiency for tryptophan conversion to NAD is 1:60, 1 mg niacin [NAD] from 60 mg tryptophan.
Turkey is an example of a food high in tryptophan; a 3-oz portion of turkey breast meat provides about 180 mg tryptophan, which could be equivalent to 3 mg niacin.
Niacin Content of Selected Foods
Food Milligrams (mg) per serving Percent DV
Beef liver, 3 ounces 14.9 93
Chicken breast, 3 ounces 10.3 64
Marinara sauce, ready to serve,
10.3 64
Turkey breast 3 ounces 10.0 63
Salmon, sockeye, 3 ounces 8.6 54
Tuna, light, canned in water, drained, 3 ounces 8.6 54
Pork, tenderloin, roasted, 3 ounces 6.3 39
Beef, ground, 90% lean, pan-browned, 3 ounces 5.8 36
Rice, brown, cooked, 1 cup 5.2 33
Peanuts, dry roasted, 1 ounce 4.2 26
Breakfast cereals fortified with 25% DV niacin 4.0 25
Rice, white, enriched, cooked, 1 cup 2.3 14
Potato, baked, 1 medium 2.3 14
Sunflower seeds, 1 ounce 2.0 13
Bread, whole wheat, 1 slice 1.4 9
Pumpkin seeds, dry roasted, 1 ounce 1.3 8
Soymilk, unfortified, 1 cup 1.3 8
Bread, white, enriched, 1 slice 1.3 8
Lentils, boiled and drained, ½ cup 1.0 6
Banana, 1 medium 0.8 5
Edamame, frozen, prepared, ½ cup 0.7 4
Raisins, ½ cup 0.6 4
Tomatoes, cherry, ½ cup 0.5 3
Broccoli, boiled, drained, chopped, ½ cup 0.4 3
Cashews, dry roasted, 1 ounce 0.4 3
Yogurt, plain, low fat, 1 cup 0.3 2
Apple, 1 medium 0.2 1
Chickpeas, canned, drained, 1 cup 0.2 1
Milk, 1% milkfat, 1 cup 0.2 1
Spinach, frozen, chopped, boiled, ½ cup 0.2 1
Tofu, raw, firm, ½ cup 0.2 1
Onions, chopped, ½ cup 0.1 1
Egg, large 0 0
Niacin is almost completely absorbed.
Niacin is metabolized to NAD.
Some excess niacin is taken up by red blood cells to form a circulating reserve pool.
The liver methylates any remaining excess to oxidation products, which are then excreted in the urine.
Unmetabolized nicotinic acid and nicotinamide may appear in the urine as well when niacin intakes are very high.
Blood niacin levels are not reliable indicators of niacin status, but the urinary excretion of its two major methylated metabolites, N1-methyl-nicotinamide and N1-methyl-2-pyridone-5-carboxamide is.
Most of the niacin absorbed is in the small intestine.
Some of niacin is absorbed in the stomach.
Recommended Dietary Allowances for Niacin:
Age Male Female Pregnancy Lactation
Birth to 6 months 2 mg 2 mg
7-12 months* 4 mg 4 mg
1-3 years 6 mg 6 mg
4-8 years 8 mg 8 mg
9-13 years 12 mg 12 mg
14-18 years 16 mg 14 mg 18 mg 17 mg
19+ years 16 mg 14 mg 18 mg 17 mg
All tissues convert absorbed niacin into its main metabolically active form: coenzyme nicotinamide adenine dinucleotide (NAD).
Tolerable Upper Intake Levels (ULs) for Niacin:
1–3 years 10 mg
4–8 years 15 mg
9–13 years 20 mg
14–18 years 30 mg
19+ years 35 mg
More than 400 enzymes require NAD to catalyze reactions in the body.
NAD catalyze reactions for enzymes more than for any other vitamin-derived coenzyme.
NAD is also converted into the coenzyme nicotinamide adenine dinucleotide phosphate (NADP), in all tissues except skeletal muscle.
NAD and NADP are required in metabolic redox processes in cells where substrates are oxidized or reduced.
NAD is primarily involved in catabolic reactions transferring potential energy in carbohydrates, fats, and proteins to adenosine triphosphate (ATP), the cell’s primary energy source.
NAD is also required for enzymes involved in critical cellular functions: , maintenance of genome integrity, control of gene expression, and cellular communication.
NADP enables anabolic reactions, such as the synthesis of cholesterol and fatty acids, and plays a citical role in maintaining cellular antioxidant function.
Deficiency associated with pellagra.
((Pellagra)) is a disease characterized by a pigmented rash or brown discoloration on skin exposed to sunlight; the skin also develops a roughened, sunburned-like appearance.
Pellagra can cause a bright red tongue and changes in the digestive tract that lead to vomiting, constipation, or diarrhea.
The neurological symptoms include: depression; apathy; headache; fatigue; loss of memory that can progress to aggressive, paranoid, and suicidal behaviors; and auditory and visual hallucinations.
As pellagra progresses, anorexia develops, and the affected individual eventually dies
Pellagra is uncommon in industrialized populations.
It is mostly limited to people living in poverty, such as refugees and displaced people who eat very limited diets low in niacin and protein.
The World Health Organization recommends treating pellagra with 300 mg/day nicotinamide in divided doses for 3-4 weeks along with a B-complex or yeast product to treat likely deficiencies in other B vitamins.
An adult has deficient niacin status when urinary-excretion rates are less than 5.8 micromol/day.
A measure of niacin status takes into account the fact that NAD levels decline as niacin status deteriorates, whereas NADP levels remain relatively constant.
Interactions with Medications
Niacin can interact with certain medications.
Isoniazid and pyrazinamide used to treat tuberculosis, are structural analogs of niacin.
They interrupt the production of niacin from tryptophan by competing with a vitamin B6-dependent enzyme required for this process.
Isoniazid can interfere with niacin’s conversion to NAD.
The ratio of NAD to NADP concentrations in whole blood x 100 below 130 suggests niacin deficiency.
The ratio of erythrocyte NAD to NADP concentrations below 1 suggests that an individual is at risk of developing niacin deficiency.
Niacin deficiency usually arises from insufficient intakes of foods containing niacin and tryptophan.
Niacin deficiency can also be caused by factors that reduce the conversion of tryptophan to niacin, such as low intakes of other nutrients.
People most likely to have inadequate niacin status:
People with undernutrition
People in poverty
People with anorexia
Alcohol use disorder
AIDS
Inflammatory bowel disease.
Liver cirrhosis often have inadequate intakes of niacin and other nutrients.
People with inadequate riboflavin, pyridoxine, and/or iron intakes.
No functional biochemical tests that reflect total body stores of niacin are available
Used to treat pellagra.
Effects all components of the lipid profile.
Lowers apolipoprotein B containing proteins and raises apolipoprotein A containing lipoproteins (HDL).
Most effective medication to increase HDL levels.
Inhibits mobilization of free fatty acids from peripheral adipose tissue to the liver and thereby reduces hepatic synthesis of VLDL and TG.
Lipid changes involve interactions of niacin with its 1 protein-coupled receptor (GPR 109A) in adipose tissue, reducing free fatty acid release (Kamanna VS, Knowles HJ).
Can increase the HDL-C by up to to 35% and reduce all cause mortality, however it may also lower LDL-C and triglycerides confounding its effect on HDL-C.
Niacin and GPR 109A receptors on epidermal Langerhans cells increase cytosolic calcium, which triggers increases in phospholipase A2 activity and prostaglandin D2 synthase, with increased mobilization of arachidonic acid into vasodilator eicosanoids and prostanoids (Maciejewski-Lenoir D, BENYO, Z, Pike NB).
Lipid lowering doses are associated with 430 to 800 fold increases in circulating levels of stable prostaglandin D2 metabolite (Morrow JD).
Very high doses of nicotinic acid (more than 100 times the RDA) taken for months or years are effective treatments for dyslipidemias.
Despite dozens of published clinical trials, experts do not agree on the value of nicotinic acid to treat cardiovascular disease, especially given its side effects, safety concerns, and poor patient compliance.
Clinical trials of nicotinic acid have examined whether it provides any additional cardiovascular protection to people taking statins.
In the largest international, multicenter, clinical trial of nicotinic acid -25,673 adults aged 50-80 years (83% men) with cardiovascular disease who were taking a statin were randomized to take 2 g/day extended-release nicotinic acid vs, a placebo
The nicotinic acid group had a mean reduction in LDL cholesterol (of 10 mg/dl) and triglycerides (of 33 mg/dl) and an increase in HDL cholesterol (of 6 mg/dl), but this group had no significant reduction in rates of major vascular events compared with the placebo , the statin-only group.
In a review that examined 23 randomized controlled trials, the use of nicotinic acid did not reduce overall mortality or cardiovascular mortality rates or the number of fatal or nonfatal myocardial infarctions or strokes.
Nicotinic acid treatment was associated with a significantly higher risk of gastrointestinal and musculoskeletal adverse events.
The nicotinic acid group had a significantly greater risk of diabetes, gastrointestinal dyspepsia, diarrhea, ulceration, bleeding events in the gut and brain, and skin rashes and ulcerations.
Four studies that examined diabetes as an outcome found that the patients taking niacin had a significantly higher risk of developing the disease.
In a review of three randomized controlled trials with 29,195 patients found that all-cause mortality increased by 10% more in those who took 1 to 3 g/day extended release nicotinic acid in addition to a statin medication than patients taking the statin alone.
In large clinical trial of 8,341 participants aged 30 to 64 years who had had one or more heart attacks were randomized to take one of five lipid-lowering medications, including 3,000 mg/day nicotinic acid, or a placebo for an average of 6.2 years:
In the study of 4300 participants with stable cardiac disease, it was found, too much niacin might increase cardiovascular risk by provoking inflammation in blood vessels.
Excess levels of breakdown products with niacin from eating too many Niacin fortified foods, over using vitamin B supplements, or having genetic variants also linked to inflammation is associated with the higher risk of major heart problems, including strokes, myocardial infarction, and death.
Taking niacin supplement is not related to lower risk of cardiovascular disease among people who also take statins, the discrepancy is termed, the niacin paradox.
Those taking nicotinic acid lowered their serum cholesterol levels by an average of 9.9% and triglyceride levels by 26.1% over 5 years of treatment.
During 5 to 8.5 years of treatment, there were significantly fewer nonfatal myocardial infarctions but more cardiac arrhythmias than those in the placebo group.
The overall rates of mortality and cause-specific mortality, including from coronary heart disease, did not decline.
But 9 years after the study ended, participants who had taken the nicotinic acid experienced significantly fewer (11%) deaths from all causes than those who had taken the placebo.
Another randomized clinical trial of 3,414 patients with established cardiovascular disease was stopped after 3 years when it was found that patients taking niacin (1,500-2,000 mg/day extended release) in addition to their cholesterol-reduction medications did not have fewer cardiovascular events than those taking medication alone, even though the niacin reduced triglyceride and LDL-cholesterol levels further and raised HDL cholesterol levels further.
The above study showed that patients taking niacin had an increased risk of ischemic stroke.
Data concludes that nicotinic acid therapy provides little if any protection from atherosclerotic heart disease, even though the therapy raises HDL cholesterol levels and lowers total cholesterol, LDL cholesterol, and triglyceride levels.
Nicotinamide does not have this effect.
Nicotinamide does not cause skin flushing and has fewer adverse effects than nicotinic acid.
Nausea, vomiting, and signs of liver toxicity can occur with nicotinamide intakes of 3,000 mg/day.
High dose nicotinic acid can increase high-density lipoprotein cholesterol levels by 10-30% and reduce low-density lipoprotein cholesterol levels by 10-25%, triglyceride levels by 20-50%, and lipoprotein(a) levels by 10-30%.
Decreases LDL-C levels by 5% to 25%, TG levels by 20% to 50%, Lp(a) by 34%, Niacin-and the TC/HDL-C ratio by 27% and increases HDL-C levels by 15% to 35%.
Despite dozens of published clinical trials, experts do not agree on the value of nicotinic acid to treat cardiovascular disease, especially given its side effects, safety concerns, and poor patient compliance.
Nicotinic acid in supplemental amounts can cause skin flushing, so some formulations are manufactured and labeled as prolonged, sustained, extended, or timed release to minimize this unpleasant side effect.
Nicotinamide does not cause skin flushing because of its slightly different chemical structure.
Serious adverse effects have occurred with high-dose nicotinic acid supplements to treat hyperlipidemias: hypotension, fatigue, impaired glucose tolerance, insulin resistance, gastrointestinal effects of nausea, heartburn, and abdominal pain. and ocular effects, such as blurred or impaired vision and macular edema.
High doses of nicotinic acid taken over months or years can also be hepatotoxic, and is more likely to occur with the use of extended-release forms of nicotinic acid.
Niacin supplements are also available in the form of inositol hexanicotinate, and do not cause flushing.
Absorption of niacin from inositol hexanicotinate varies widely but on average is 30% lower than from nicotinic acid or nicotinamide, which are almost completely absorbed.
Niaspan and generic niacin ER, are prescription medicines, providing 500-1,000 mg extended-release nicotinic acid for treating high blood cholesterol levels.
Most people consume more than the RDA for niacin.
National Health and Nutrition Examination Survey (NHANES) found that the average daily niacin intake from foods and beverages was 21.4 mg for ages 2–19: In adults, the average daily niacin intake from foods and beverages was 31.4 mg in men and 21.3 mg in women.
NHANES found that only 1% of adults had intakes of niacin from foods and beverages below the recommended daily allowance.
Among all racial and ethnic groups, Hispanics have the greatest prevalence, 1.3%, of niacin intakes below the daily allowance.
About 21% of all individuals aged 2 and older take a dietary supplement containing niacin
The proportion of users increases with age.
Supplement use doubles or triples total niacin intakes compared with intakes from diet alone.
Facial and truncal flushing occurs in most patients causing more than 25% of patients to discontinue therapy.
Flushing leads to 20-30% of patients dropping out of taking the drug.
While no adverse effects have been reported from the consumption of naturally occurring niacin, high intakes of both nicotinic acid and nicotinamide taken as a dietary supplement or medication can cause adverse effects.
Thirty to 50 mg nicotinic acid or more typically causes flushing.
With flushing the skin on the patient’s face, arms, and chest turns a reddish color because of vasodilation of small subcutaneous blood vessels.
Skin flushing can be accompanied by burning, tingling, and itching sensations.
Skin flushing and associated symptoms are typically transient.
Skin flushing can occur within 30 minutes of intake or over days or weeks with repeated dosing.
Flushing can be accompanied by headache, rash, dizziness, and/or a decrease in blood pressure.
Flushing effects can be reduced the by taking nicotinic acid supplements with food, increasing the dose over time, or awaiting a natural tolerance.
Approximately 53% of patients did not reach maintenance doses of 1 gm or higher, and 92% did not reach doses of 2 gm (Kamal-Bahl SJ).
Extended release niacin lowers the risk of flushing.
Aspirin or NSAID taken 30 minutes to 1 hour prior the taking niacin will decrease the severity of flushing.
After 6 years of treatment with niacin the incidence of non-fatal myocardial infarction is reduced by 26% and cerebrovascular events are reduced by 24%.
Reduces risk of myocardial infarction by 27%, and risk of all cause mortality by 11%, and is associated with angiographic benefits.(Canner PL,)
Extended release niacin lowers the risk of flushing.
The Arterial Biology for the Investigation of the Treatment Effects Reducing Cholesterol 6-HDL and LDL (ARBITER 6-HALTS) study compared either niacin or ezetimibe added to a long-term statin therapy on carotid intima-media thickness over a 14 month period:the use of extended release niacin causes significant regression in the carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe.
In the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High triglycerides: Impact on Global Health Outcomes (AIM-HIGH). Trial randomized 3414 patients to receive simvastatin plus extended-release niacin, or placebo: at two years niacin plus simvastatin had an increase of HDL-C from 35 mg/dL to 42 mg/dL, and reduced LDL-C from 74 to 62 mg/dL, but there was no difference in the primary and point which was the first event of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom driven coronary or cerebral revascularization.
With stable nonacute cardiovascular disease and LDL-C levels achieved and maintained below 70 mg/dL no clinical benefit is it obtained from the addition of niacin to statin therapy.
The use of extended release niacin and fenofibrate have not provided mortality benefit when added to statin therapy, despite widespread use.
Niacin effectively lowers triglyceride levels but does not lower the risk of coronary heart disease and increases the incidence of infection, bleeding and diabetes.
In a metaanalysis among patients with or at high risk for atherosclerotic cardiovascular disease, niacin does not reduce mortality (Garg A)
Nonstatin therapies, compared with or in addition to statin therapy, do not provide atherosclerotic cardiovascular disease risk-reduction benefits that outweigh the potential harms of their adverse effects.
Nicotinic acid supplementation improves blood lipid profiles but has no significant effects on risk of cardiovascular events.
In the above study niacin was not associated with significant reduction in recurrent cardiovascular events such as myocardial infarction , stroke or revascularizations.
It is associated with increased risk of new onset or worsening diabetes with skin, gastrointestinal, and muscular skeletal adverse effects (Gary A).
In the above study the addition of niacin to statin therapy was associated with a significant increase in serum levels of HDL-C and a non-significant decrease in total cholesterol and LDL-C compared with placebo.
Large doses of nicotinic acid can raise blood glucose levels, increase insulin resistance and increasing hepatic production of glucose.
Metabolic analysis of fasting patients in a prospective discovery of niacin metabolism was associated with incident major adverse cardiovascular events (MACE).