Key Takeaways (expand)
- Niacin, or vitamin B3, is a water-soluble vitamin that can be produced from the amino acid tryptophan.
- The term niacin technically refers to several different dietary precursors to the coenzyme nicotinamide adenine dinucleotide; these precursors include nicotinic acid, nicotinamide (or niacinamide), and nicotinamide riboside.
- As with other B vitamins, niacin is involved in energy metabolism, neurotransmitter production, and cellular function.
- Niacin’s most noteworthy function is in forming two important coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
- Over 400 enzymes require NAD and NADP to carry out their activities, mostly for oxidation-reduction reactions.
- NAD is mainly used in catabolic reactions (especially the breakdown of fats, carbohydrates, proteins, and alcohol); it’s also needed for certain enzymes involved in DNA repair, making it critical for genome stability.
- NADP is involved in anabolic reactions (including synthesizing fatty acids, cholesterol, bile acids, stress hormones, and sex hormones), as well as for regenerating various components of antioxidant and detoxification systems.
- Via its coenzyme role, niacin plays an important role in energy production: during the final step of the Krebs cycle, the reduced form of NAD (NADH) helps deliver electrons to the electron transport chain, leading to ATP production—the energy currency of cells.
- Niacin may play a role in cancer prevention (including leukemia, skin, mouth, breast, throat, and esophageal cancers), largely by influencing pathways that protect DNA and chromosomes from damage.
- High doses of niacin may be therapeutic for cardiovascular disease and hyperlipidemia, with studies showing it can improve blood lipid profiles, reduce plaque formation, and improve endothelial function.
- Human trials have shown that among people with previous cardiovascular events, niacin supplementation can reduce the risk of stroke, heart attack, and overall mortality.
- High-dose niacin appears associated with better health outcomes in HIV patients and schizophrenics.
- Higher blood levels of niacin are associated with a lower risk of developing type 1 diabetes—possibly due to its ability to protect beta-cells from damage, as well as improve their functioning.
- Although true niacin deficiency is uncommon in the modern world, when it does occur, it can lead to reduced cold tolerance, slower metabolism, and most famously, pellagra—a disease characterized by a range of physical and neurological problems including dermatitis, photosensitivity, insomnia, hair loss, weakness, delirium, irritability, anxiety, memory loss, restlessness, and depression.
- Rich sources of niacin include red meat, poultry, salmon, tuna, shellfish, yeast, organ meats, mushrooms, leafy green vegetables, nuts, seeds, and legumes.
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Niacin, also called vitamin B3, is a water-soluble vitamin that can be manufactured from the amino acid tryptophan. The term niacin actually refers to a number of dietary precursors to the coenzyme nicotinamide adenine dinucleotide—including nicotinic acid, nicotinamide (sometimes called niacinamide), and nicotinamide riboside. It was first synthesized (in the form of nicotinic acid) from the oxidation of nicotine in 1867, long before the concept of vitamins even existed! It wasn’t until 70 years later, after ongoing efforts to understand and treat a disease called pellagra (which we now know is caused by niacin deficiency), that niacin was finally isolated by the biochemist Conrad Elvehjem and initially named the “pellagra-preventing factor” or vitamin P-P. The nutrient was later renamed niacin from a combination of letters in nicotinic acid and vitamin. And, in 1955, when scientists discovered that consuming large amounts of niacin could reduce cholesterol levels, niacin became the first-ever lipid lowering drug!
Like other B vitamins, it plays an important role in energy metabolism—breaking down the carbohydrates, fat, and protein we eat for use as fuel (hence why B-complex vitamins are often nicknamed the “energy vitamins!”), as well as neurotransmitter production, cellular function, and a wide variety of organ functions.
Good food sources of niacin include red meat, poultry (including chicken and turkey), some seafood (especially salmon and tuna), yeast, organ meat, shellfish, mushrooms, leafy green vegetables, nuts, seeds, and legumes. Many grains and breakfast cereals are also fortified with niacin.
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The Biological Roles of Vitamin B3 (Niacin)
Niacin is used to form two extremely important coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Over 400 enzymes are dependent on NAD and NADP, mostly for accepting or donating electrons for oxidation-reduction reactions (which involve the transfer of electrons across a membrane in the mitochondria). NAD is mostly used in catabolic reactions where carbohydrates, fats, proteins, and alcohol are broken down for energy. And, NAD is the sole substrate for the sirtuins and PARP enzymes involved in DNA repair, making this coenzyme (and by extension, niacin) pivotal for genome stability. It also serves as a ligand, binding to membrane receptors of the P2Y subclass (which mediate responses like immune signaling, neuronal activity, vasodilation, and blood clotting).
Meanwhile, NADP has a greater role in anabolic reactions, especially in synthesizing fatty acids, cholesterol, bile acids, stress hormones, and sex hormones. It’s also used for regenerating different components of detoxification and antioxidant systems, and in cytochrome P450 metabolism of endobiotics and xenobiotics.
Like other B vitamins, it also plays an important role in energy metabolism—particularly the second stage of cellular respiration, called the Krebs cycle or citric acid cycle. The Krebs cycle is an incredibly important series of chemical reactions that all aerobic organisms use to generate energy, through an eight-step process taking place in a cell’s mitochondria. During this cycle, acetate (in the form of acetyl CoA) derived from carbohydrates, fat, or protein undergoes a series of redox, dehydration, hydration, and decarboxylation reactions to produce adenosine triphosphate (ATP), the energy currency for all cells—as well as the waste product carbon dioxide, and reduced forms of NADH and FADH2 (which can then be converted into yet more ATP in the last step of the Krebs cycle: oxidative phosphorylation in the electron transport chain). This is complex biochemistry, but the important part here is that there are a whole lot of chemical reactions required to produce energy for our cells, and B vitamins are essential for that process!
Niacin’s specific role in this cycle is through the formation of NAD, which gets reduced to NADH after picking up two hydrogen electrons. In turn, NADH serves as an energy shuttle to deliver electrons to the electron transport chain in the final step of the Krebs cycle, powering the production of two or three molecules of ATP. So, niacin is absolutely vital for the production of cellular energy!
Drug Interactions with Vitamin B3 (Niacin)
Niacin also has some important interactions with drugs. For example, niacin is often prescribed in conjunction with statins, but this co-administration can sometimes increase the risk of rhabdomyolosis—a condition where muscle cells break down, causing a release of enzymes and electrolytes into the blood and sometimes leading to kidney failure. Other studies suggest that combining antioxidant supplementation (vitamin C, vitamin E, selenium, and beta-carotene) with niacin-statin therapy (particularly nicotinic acid along with the statin simvastatin) may reduce the effectiveness of the niacin-statin therapy, although the mechanism is currently unknown. Combining nicotinic acid with cholestyramine or colestipol (bile acid sequestering drugs) or gemfibrozil (a cholesterol-lowering drug) may increase the risk of myopathy, and combining nicotinic acid with paracetamol, amiodarone, or carbamazepine may increase the risk of liver toxicity. And, taking estrogen or estrogen-containing contraceptives can enhance the efficiency of synthesizing niacin from tryptophan and reduce the body’s dietary needs for this nutrient.
Vitamin B3 (Niacin) in Health and Disease
Vitamin B3 (niacin) may have protective effects for a variety of chronic diseases. Niacin has potential anti-cancer properties, due to its ability to influence pathways that protect chromosomes and DNA from damage; human studies show it may help protect against leukemia, skin cancer, breast cancer, throat cancer, mouth cancer, and esophageal cancer. It also has established blood-lipid-lowering effects, and may benefit cardiovascular health through several other avenues as well—including reducing plaque buildup and improving endothelial function. It may also help improve beta-cell function in people at risk of type 1 diabetes, as well as benefit patients with HIV and schizophrenia.
Niacin and Cancer
Some evidence suggests niacin could play a role in cancer prevention—largely through its influence on mechanisms that protect DNA and chromosomes from damage. By helping maintain an abundant pool of NAD, niacin allows important cancer-protective reactions to take place, including poly ADP-ribosylations catalyzed by PARP enzymes (which are critical for responding to DNA injury). NAD depletion has also been shown to reduce levels of the tumor suppressor protein p53 in human breast cells, lung cells, skin cells, and rodent bone marrow cells—suggesting that adequate niacin is involved in keeping this protein at high enough levels to do its anti-cancer work (including initiating DNA repair and inducing apoptosis)!
Across studies, niacin has also been shown to affect leukemia risk in rats, to potentially reduce the risk of mouth, throat, and esophageal cancers in humans (a 40% decrease in cancer risk with each 5.2 – 6.2 mg increase in daily niacin intake, according to case-control studies), and protect against squamous-cell and basal-cell carcinomas in people with a history of nonmelanoma skin cancers (a 30% and 20% reduction in risk, respectively, after a year of daily nicotinamide supplementation). And even in people without a history of skin cancer, large prospective cohort studies have found that adults with the highest versus lowest intake of niacin appear to have a lower risk of developing squamous-cell carcinoma over the course of many years.
Niacin and Cardiovascular Disease
Very high doses of niacin have also been used for the treatment of hyperlipidemia (high cholesterol and triglycerides) and cardiovascular disease; in fact, this is a common practice that has been employed by doctors since the 1950s! More specifically, niacin supplementation (in the form of nicotinic acid) can reduce serum very low-density lipoprotein (VLDL) cholesterol and LDL cholesterol, lower triglycerides and lipoprotein(A) (a cholesterol-transporting protein associated with higher likelihood of plaque and blood clots forming in the arteries), and increase HDL cholesterol (AKA “good”cholesterol)—while also helping reduce plaque formation in our blood vessels.
These lipid-therapeutic properties still aren’t fully understood, but we do know that they’re partly mediated through the activation of G protein-coupled receptors—particularly hydroxycarboxylic acid receptor 2 (HCA2) and hydroxycarboxylic acid receptor 3 (HCA3), which suppress the release of free fatty acids from body fat, in turn reducing the amount of building blocks available for the liver to use for cholesterol synthesis. This reduction in free fatty acids also suppresses the expression of certain proteins in the liver (apolipoprotein C3 and PPARg coactivator-1b), leading to reduced production and increased turnover of VLDL. When it comes to niacin’s effects on HDL, it’s much more of a mystery! However, niacin has been shown to raise levels of apolipoprotein A1 (a component of HDL) by preventing its breakdown, and also inhibits the uptake of HDL by the liver by suppressing production of the cholesterol ester transfer protein gene.
Additionally, niacin may have lipid-modulating effects through other mechanisms, such as lowering inflammation, reducing oxidative stress, and regulating cell adhesion, differentiation, and migration. A number of randomized controlled trials have even shown that niacin supplementation can significantly improve flow-mediated dilation (a surrogate measure of endothelial function) in people who either have cardiovascular disease or are at high risk of developing it.
Some clinical trials, especially in people with previous cardiovascular events, have shown that niacin supplementation (2 – 3 grams a day) reduces the risk of stroke, the recurrence of myocardial infarctions, and overall mortality. That being said, despite its beneficial effects on blood lipid profiles and the success of a handful of trials, systematic reviews haven’t found an overall protective effect of prescription niacin on all-cause mortality, heart attacks, strokes, or overall heart disease deaths.
Niacin and Acne
Niacin may have a beneficial effect on acne. Although most trials have used topically applied niacin for the treatment of acne, a 2017 review found that oral niacin (in the form of nicotinamide) significantly improved patients’ acne compared to baseline.
Niacin and Fatigue
Niacin may also be beneficial for fatigue, due its role in energy production (particularly as NAD). However, more studies are needed in humans to test the effects of dietary niacin, and at what intakes, on symptoms of physical fatigue.
Niacin and Alzheimer’s Disease
Some research has pointed to potential protective effects of niacin on Alzheimer’s disease. For example, a 2004 prospective study of older adults found that compared to people with the lowest quintile of niacin intake, those with higher intakes had a 40 to 70% lower risk of developing Alzheimer’s disease over time, even after adjusting for potential confounders. Likewise, higher intake of niacin from food was associated with slower rates of cognitive decline each year.
Animal models of Alzheimer’s disease have also shown that niacin supplementation can beneficially affect the hub genes and pathways involved in the cognition. Although the findings would need to be replicated in humans, this suggests niacin could be useful in the prevention and treatment of Alzheimer’s.
Niacin and Other Health Conditions
Research also shows that treatment with high-dose niacin could be associated with better outcomes in patients with HIV (including cardiovascular disease risk among this population), as well as in patients with schizophrenia.
Studies have shown an association between serum nicotinamide and reduced risk of developing type 1 diabetes, with animal experiments also showing that administration of nicotinamide can protect beta-cells from damage. Human studies have likewise shown that niacin supplementation can improve beta-cell function among people at high risk of type 1 diabetes (as well as improving inflammation-related parameters), but failed to show a clear benefit for improving glycemic control or reducing actual disease onset.
Didn’t know vitamin B3 was this amazing? Maybe your friends will enjoy this too!
Health Effects of Vitamin B3 (Niacin) Deficiency
As with other B vitamins, true clinical vitamin B3 deficiency isn’t common in the modern world, and rarely happens in isolation (that is, if you’re deficient in niacin, you’re probably deficient in other water-soluble vitamins too!). When it does occur, niacin deficiency is generally a result of poor dietary intake, alcoholism, defective tryptophan absorption, long-term chemotherapy use, a high consumption of non-nixtamalized corn (due to its niacin not being bioavailable), or metabolic disorders.
Mild niacin deficiency can lead to slower metabolism and reduced cold tolerance. But, the most famous result of niacin deficiency is a disease called pellagra—characterized by dermatitis, diarrhea, photosensitivity, insomnia, hair loss, tongue inflammation, weakness, and neurological changes like dementia, delirium, irritability, anxiety, memory loss, restlessness, depression, apathy, and other emotional disturbances. Although less common today, pellagra was endemic in Europe in the 1700s due to widespread corn cultivation: while corn in the Americas was traditionally prepared with methods that made the niacin become bioavailable (namely, a process called nixtamalization, which involves pre-treating the corn with an alkali ingredient like lime), those methods didn’t carry over to Europe, and corn-eating populations were left unknowingly niacin deficient.
Fascinatingly, there’s reason to believe that niacin deficiency contributed to origin of vampire folklore: pellagra symptoms resemble many attributes ascribed to vampires (including sensitivity to sunlight, insomnia, erratic behavior, aggression, and delirium), and vampire legends famously arose from corn-eating areas of Eastern Europe around the same time pellagra was striking those regions!
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Problems From Too Much Vitamin B3 (Niacin)
It’s worth noting that while reaching side-effect-causing levels of niacin is almost impossible through diet alone, high therapeutic doses (typically 1 to 3 grams daily) can produce side effects such as transient flushing, severe itching, rashes, low blood pressure, headache, and and gastrointestinal upset (like nausea and vomiting). These symptoms can often be reduced by consuming niacin supplements with a meal, slowly increasing the dosage over time, or choosing slow-release forms of niacin. Supplemental doses as low as 750 mg per day of nicotinic acid have even led to liver damage in some people. And, severe hepatitis has been linked to doses of 3 to 9 g daily taken for many months or years as a high cholesterol treatment. Studies have even suggested a potential increased risk of new-onset type 2 diabetes as a result of such treatments. (The diabetes-promoting effect may be due to large doses of niacin decreasing insulin sensitivity and impairing glucose tolerance, leading to elevated blood sugar and spurring the development of diabetes in people who were already predisposed.)
Likewise, people with gout, peptic ulcer disease, a history of liver disease or abnormal liver function, cardiac arrhythmias, migraines, alcoholism, or inflammatory bowel disease may be more likely to experience adverse reactions to niacin supplementation than the rest of the population, and nursing women are advised to avoid prescription niacin products due to unknown effects on the nursing infant.
So, while getting abundant dietary niacin is an excellent goal, caution is warranted when consuming large therapeutic doses, and should only be done under the guidance of a healthcare provider!
How Much Vitamin B3 (Niacin) Do We Need?
The recommended daily allowance (RDA) for niacin is 14 mg per day for women (18 mg daily while pregnant, and 17 mg daily while breastfeeding/lactating) and 16 mg of niacin per day for men. Most people are likely meeting this RDA as long as they consume adequate animal protein: the average dietary intake of niacin is approximately 25 mg per day, and the foods highest in niacin are also rich in the amino acid tryptophan, which can can be further converted into niacin.
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Nutrient Daily Values
Nutrition requirements and recommended nutrient intake for infants, children, adolescents, adults, mature adults, and pregnant and lactating individuals.
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Best Food Sources of Vitamin B3 (Niacin)
The following foods have high concentrations of niacin, containing at least 50% of the recommended dietary allowance per serving, making them our best food sources of this valuable B-vitamin!
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Good Food Sources of Vitamin B3 (Niacin)
The following foods are also excellent or good sources of niacin, containing at least 10% (and up to 50%) of the daily value per serving.
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