Niacin (Vitamin B3), also known as “nicotinic acid,” is a colorless, hydrophilic derivative of pyridine and an essential dietary nutrient for humans. Inadequate dietary intake of niacin is the root cause of a medical condition known as “pellagra,” characterized by a host of neuropsychiatric symptoms including: anxiety, amnesia, brain fog, cognitive impairment, delirium, depression, and fatigue. Failure to correct a niacin deficiency not only exacerbates the aforementioned symptoms, but could lead to death.
From the early to mid 1900s, upwards of 3 million Americans were diagnosed with pellagra (niacin deficiency) causing over 100,000 deaths. Researchers eventually discovered that “pellagra” could be cured by simply correcting the underlying niacin deficiency (via dietary modifications or supplementation). This correction reversed neuropsychiatric symptoms, well-known physical symptoms associated with deficient niacin including: diarrhea, mouth inflammation, lesions, pigmentation changes, and thickening of skin.
Daily recommended dietary intake of niacin ranges between 14 and 18 mg/day for adults. Ensuring that dietary niacin needs are met can prevent conditions like pellagra, increase BDNF levels, and favorably modulate cholesterol. For these reasons, it’s no surprise that many individuals regularly take niacin supplements and/or pharmaceutical grade niacin.
Though proper niacin supplementation can provide benefit to those who are deficient, excess niacin may trigger adverse effects. Abnormally high vitamin B3 intake (usually from supplements) can cause what’s known as a “niacin flush” – feeling warm, turning red, and experiencing itches and/or tingles throughout the body. For this reason, some users may cease supplementation, only to wonder how long exogenous niacin will remain in their system.
How long does Niacin stay in your system?
Assuming you had an unfavorable reaction to niacin supplementation, you’re probably wondering how long it’ll take before the excess niacin is cleared from systemic circulation. To understand how long niacin (or nicotinic acid) will stay in your plasma, it is necessary to examine its elimination half-life. Most sources document niacin’s elimination half-life between the range of 20 and 60 minutes (for an average of ~45 minutes).
This suggests that in nearly all users, 50% of a niacin dosage should be out of your plasma in less than an hour after you take it. With this elimination half-life, we can estimate that it’ll likely take between 1.83 and 5.5 hours to completely clear niacin from your plasma. Based on the 45 minute average, it is likely that niacin should be out of your system within 4.13 hours after its ingestion.
However, just because niacin is likely to be out of your system in under 6 hours post-ingestion does not mean that its metabolites will also have been eliminated. Niacin forms several metabolites including: nicotinamide, nicotinuric acid (NUA), and nicotinamide adenine dinucleotide (NAD). Of these metabolites, nicotinamide exhibits a longer half-life than its parent (niacin) ranging from 2 to 8 hours (for an average of 5 hours).
The half-life of nicotinamide appears to be dose dependent, in other words, if you ingested a significant dosage of niacin, more nicotinamide will form and the elimination half-life may be closer to 8 rather than 2 hours. In any regard, the half-life range of 2 to 8 hours suggests that nicotinamide will be eliminated from plasma circulation between 11 hours and 1.83 days post-ingestion. Most users should therefore have eliminated niacin and its metabolites within 2 days (48 hours) of discontinuation.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/nicotinic_acid
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/nicotinamide
- Source: http://www.ncbi.nlm.nih.gov/pubmed/4287855
Variables that influence how long Niacin stays in your system
Though most users will have eliminated niacin from their system in less than 6 hours post-ingestion, and its metabolites in less than 2 days after ingestion, not everyone will experience the exact same elimination speed. Some users may eliminate niacin and its metabolites quicker than others. Differences in elimination speed can usually be explained by variables such as: format of niacin, individual attributes (e.g. overall health), niacin dosage, and frequency of administration.
Niacin Format (Vitamin B3)
There are several formats of niacin available for supplementation and/or prescription. Examples of popular niacin formats include: Niacor, Niaspan, Slo-Niacin, Inositol Hexanicotinate, as well as standard Niacin supplements. Understand that the format in which Niacin is administered may affect how long it stays in your system. The format doesn’t affect the half-life of niacin itself, but may modify absorption times – leading to short/long systemic circulation.
Niacor or Niaspan: Niacor and Niaspan are pharmaceutical grade Niacin formulations approved by the FDA for the modulation of cholesterol. Each is specifically thought to reduce bad cholesterol (LDL) and increase good cholesterol (HDL), thereby normalizing one’s cholesterol. The major difference between Niacor and Niaspan is that Niacor is manufactured in an “immediate-release” (IR) format, whereas Niaspan is delivered as an “extended-release” (ER) format.
The half-life of Niacor isn’t different from standard non-pharmaceutical niacin and is estimated at 45 minutes. The half-life of Niaspan is similar, but keep in mind that niacin from Niaspan is delivered for up to 12 hours. This means that once 12 hours have passed, you can expect another 4.13 hours to eliminate niacin from systemic circulation. This means that Niaspan users may have niacin in their plasma for up to 17 hours of the day.
Slo-Niacin: This format of niacin is manufactured in 500 mg doses and provides a controlled-release delivery via a polygel tablet. It is unknown as to how long the delivery period lasts as it isn’t public knowledge. Therefore, it can be speculated that Slo-Niacin is likely absorbed at a slower rate than a standard immediate-release niacin, but absorption may be quicker than an extended release drug like Niaspan. The niacin delivered from Slo-Niacin is unlikely to linger in your system for longer than 17 hours after its ingestion.
Inositol Hexanicotinate (IHN): This is an esterified form of niacin sold over-the-counter and marketed as having “no flushing” as a side effect. Inositol hexanicotinate is manufactured in 250, 500, and 1000 mg tablets. Despite its over-the-counter availability, it is believed that inositol hexanicotinate is ineffective or inferior to pharmaceutical grade niacin formulations for the treatment of hyperlipidemia (high cholesterol).
Its elimination half-life reportedly ranges between 1.07 and 3.93 hours in humans. This suggests that it may take between 5.89 and 21.62 hours to eliminate from the plasma after administration – longer than standard niacin supplements. If you take this format of supplement to bolster your niacin, expect it to stay in your system for a longer duration than if you were taking a standard niacin supplement.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23347001
Nicotinamide: This is a metabolite of niacin that is known to exhibit a longer half-life than its parent (niacin). Some individuals may purchase and use nicotinamide supplements, not realizing that the half-life of nicotinamide ranges from 2 to 8 hours and is dose-dependent. This means that it could take nearly 48 hours to eliminate a high dose of nicotinamide from your system after ingestion.
Niacin (Standard): Standard forms of niacin sold over-the-counter as dietary supplements should be rapidly absorbed and eliminated from your plasma quickly. Expect a niacin supplement to be eliminated from your plasma in less than 6 hours after administration. Though nicotinamide metabolites (nicotinamide) will form upon metabolism of niacin, these metabolites should be out of your plasma in under 1.83 days.
Daily Dosage (High vs. Low)
The amount of niacin a person ingests may affect how long it stays in systemic circulation (along with nicotinamide metabolites). Certain individuals may take niacin doses as low as 500 mg per day with the intention of improving cholesterol biomarkers, vision, and/or erectile dysfunction. At such a low dose, niacin is easily absorbed, metabolized, distributed, and excreted from the body.
Individuals taking extremely high doses such as between 4 and 12 grams to treat heart disease and/or improve arterial health – may exhibit longer elimination half-lives of niacin. At high doses, niacin is understood to tax hepatic pathways within the liver, possibly causing hepatotoxicity. Increased taxation of these pathways will likely protract elimination half-life among high dose users compared to those taking low doses.
The hepatic burden incurred from high doses of niacin may lead to slower metabolism and elevated plasma concentrations of unchanged niacin. This may prolong its elimination half-life to a significant extent. It should also be noted that high doses of niacin will yield greater quantities of metabolites (e.g. nicotinamide) compared to lower doses.
Since niacin metabolites are subject to renal excretion, the greater the quantity of these metabolites, perhaps the less efficient they’ll get eliminated via the kidneys. High levels of metabolites may accumulate in renal pathways, some of which may be subject to reabsorption and recirculation throughout a user’s system, further prolonging elimination. The lower the dose of niacin you ingest, the more efficient you can expect to metabolize and excrete it.
If we were to hypothetically assume that two individuals simultaneously ingested the same format of niacin at equipotent dosages, one user would likely eliminate niacin quicker from his/her system than the other. In this case, interindividual differences in elimination times can be explained by factors such as a user’s: age, body mass, hepatic function, and renal function. When contemplating how long niacin is likely to remain in your system, these factors may be helpful to consider.
Age: It is possible that a user’s age may affect how long niacin stays in systemic circulation post-ingestion. Healthy young adults supplementing with niacin may efficiently metabolize and excrete it, whereas elderly adults may exhibit slower niacin metabolism and excretion. Prolonged elimination half-life among elderly individuals may result from: alterations in volume of distribution, concomitant medications, diminishing hepatic function, decreased renal function, and slower metabolic rate.
Body mass + Fat (%): A niacin user’s body mass index (BMI) and fat percentage may affect how long niacin stays in his/her system after ingestion. Individuals with a high body fat percentage are thought to eliminate niacin quicker from systemic circulation than those with low body fat. This is due to the fact that niacin is water soluble (hydrophilic) and has an affinity for water stores within the body.
A high body fat percentage is usually associated with less muscle tissue, and ultimately fewer water stores. Fewer water stores inhibit niacin retention and essentially forces it from out of systemic circulation at a faster pace than usual. Conversely, individuals with lower BMIs and less fat tend to carry more muscle tissue (and water stores), and retain niacin for a longer duration than obese counterparts.
Genetics: Among those taking extremely high doses of supplemental niacin, it is possible that functionality of hepatic CYP450 isoenzymes may be compromised. Specifically, high dose niacin is known to inhibit CYP2D6 and its metabolite, nicotinamide, inhibits CYP3A4. For this reason, it is necessary to consider that polymorphisms of CYP2D6 and possibly CYP3A4 alleles may affect niacin’s metabolism.
If you are a high dose user and are considered a CYP2D6 poor or intermediate metabolizer (in that you have non-functional CYP2D6 alleles), plasma concentrations and elimination half-life of niacin may be increased. If you are considered an ultrarapid or extensive CYP2D6 metabolizer, you may eliminate niacin and its metabolites faster and with greater efficiency than other high dose users.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15081432
Hepatic function: It is unclear as to whether hepatic impairment extends the elimination half-life of supplemental niacin. That said, it is likely that hepatic dysfunction has an impact on niacin metabolism due to the fact that niacin is metabolized within the liver. Therefore, it would be expected that among individuals with hepatic impairment, niacin is less efficiently metabolized, its plasma concentrations are greater, and elimination is prolonged.
The degree of hepatic impairment (e.g. mild, moderate, severe), the dosage of niacin ingested, as well as the format of niacin (e.g. instant-release vs. sustained-release) – may have a symbiotic relationship in regards to its half-life. The greater the severity of hepatic impairment and dosage (especially with sustained-release formats), the longer the elimination half-life of niacin is likely to be.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1626557
Metabolic rate: An individual’s BMR (basal metabolic rate) may affect how long niacin remains in systemic circulation. Those with high BMRs are known to burn more energy at rest than those with lower BMRs. Burning more energy at rest is associated with faster metabolism and excretion of exogenous substances such as supplemental niacin. If you know that you have a high metabolism, niacin may be eliminated (at least slightly) quicker than someone with a lower metabolism.
Other drugs: Co-administration of pharmaceutical drugs and/or supplements may alter the kinetics of niacin, especially high-dose niacin. High doses of niacin are believed to undergo hepatic metabolism via various CYP450 isoenzymes such as CYP2D6 and CYP3A4. If you’re taking another drug along with niacin that inhibits and/or induces activity of the aforementioned isoenzymes, niacin may be eliminated quicker or slower than usual from your plasma.
Drugs that inhibit functionality of CYP2D6 may increase plasma concentrations of niacin, ultimately prolonging its elimination half-life. Oppositely, drugs that induce function of CYP2D6 may create more metabolites and decrease plasma concentrations of niacin. If you took an inhibitor along with high-dose niacin, plasma retention may be longer, whereas if you took an inducer with high-dose niacin, plasma retention may be shorter.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15081432
Renal function: Most medical literature suggests that niacin-based drugs and supplements should be administered with caution among those with renal impairment. After niacin is metabolized and distributed, its metabolites are eliminated via various pathways in the kidneys. Efficiency of metabolite excretion may be compromised among those with impaired renal function.
Typically, the greater the severity of a person’s renal impairment, the longer they’re likely to retain niacin metabolites. Someone with severe renal impairment (e.g. cirrhosis) may retain niacin for a substantially longer duration than a user with normative renal function. Renal impairment may lead to metabolite accumulation, reabsorption, and redistribution – all of which may prolong the excretion process.
Sex: Studies have shown that steady-state levels of niacin-based pharmaceuticals such as Niaspan are higher in females than males. It is believed that elevated plasma concentrations among women stem from differences in metabolic rate and/or volume of distribution. Though elevated plasma concentrations do not always prolong elimination half-life of substances, they sometimes do. For this reason, it could be expected that at standard doses, elimination half-life of niacin may be longer in women than men.
- Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020381s020lbl.pdf
Niacin: Absorption, Metabolism, Excretion (Details)
Following oral administration of niacin, between 60 and 76% of a dose is rapidly absorbed via the gastrointestinal (GI) tract. It then subject to extensive hepatic first-pass metabolism in which it undergoes glycine conjugation to form the metabolite nicotinuric acid (NUA). A small amount of nicotinuric acid is known to be reversible prior to excretion, getting converted back into its parent “niacin.”
Another pathway in the liver facilitates the conversion of niacin to the metabolite nicotinamide adenine dinucleotide (NAD). This leads to the synthesis of the metabolite nicotinamide, which undergoes additional metabolism to form N-methylnicotinamide (MNA) and nicotinamide-N-oxide (NNO). N-methylnicotinamide is metabolized to form N-methyl-2-pyridone-5- carboxamide (2PY) and to a lesser extent, N-methyl-4-pyridone-5-carboxamide (4PY).
After absorption, niacin and its metabolites appear to concentrate within hepatic, renal, and adipose tissue. The elimination half-life of niacin appears to be somewhat dose-dependent, but averages around 45 minutes. The half-life of its nicotinamide metabolite is also dose-dependent and averages around 5 hours. Therefore, we can expect that niacin should be eliminated from systemic circulation in around 4.13 hours, whereas its nicotinamide metabolite may take a little over 1 day for complete elimination.
Once metabolites are cleared from the plasma, they are excreted by the kidneys and appear within the urine. Quantities of urinary metabolites may be subject to variation based on dosage ingested. That said, approximately 70% of a dosage can be recovered in urine as: 2PY (38%), MNA (16%), NUA (11.6%), unchanged niacin (3-12%), NAM, and NNO.
Urinary half-lives of 2PY and MNA are between 12 and 13 hours. With this information, we can estimate that niacin users should have completely excreted its metabolites in less than 3 days of usage.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/nicotinic_acid
- Source: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020381s020lbl.pdf
- Source: http://www.sunovion.ca/monographs/niaspan.pdf
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17725178
Tips to clear Niacin from your system
If you’ve been taking niacin for awhile and want to ensure that its out of your system, the best thing you can do is simply discontinue supplementation. Upon discontinuation of supplemental niacin, your body will rapidly clear it from the plasma. After you’ve discontinued, you may want to consider some supplements to aid in hepatic detoxification and renal excretion of niacin metabolites. Prior to implementing any of the suggestions, verify their safety and alleged efficacy with a medical professional.
- Discontinuation: Unless you overdosed on niacin and were using it improperly (without medical supervision), there’s really no need to take extra steps to make sure that it gets cleared from your system. Simply discontinuing niacin supplements will allow your body to eliminate any circulating niacin within 6 hours of your last dose. Niacin metabolites (e.g. nicotinamide) will be eliminated between 11 and 44 hours thereafter.
- Activated charcoal: Individuals that took too much niacin and want to eliminate it from their system rapidly may want to consider supplementation with activated charcoal. Activated charcoal has a negative electric charge and binds to unmetabolized drugs and supplements via adsorption. Should you have any unmetabolized niacin lingering in your liver, activated charcoal will ensure proper detoxification.
- Calcium-d-glucarate: After niacin is metabolized, its metabolites (e.g. nicotinamide) are excreted via renal pathways. These renal pathways may become overwhelmed among individuals taking high doses of niacin, other drugs, and/or among those exposed to dietary toxins. Calcium-d-glucarate is a beneficial supplement to consider in that it functions as a beta-glucuronidase inhibitor, clearing molecular build-up within detoxification pathways. Think of this supplement as helping your kidneys clear excess waste at a faster pace.
How long do you think Niacin stayed in your system?
If stopped taking niacin, share a comment mentioning how long it took for adverse effects to subside after your final dose. Keep in mind that just because you may have experienced lingering effects from niacin supplementation does not necessarily indicate that niacin or its nicotinamide metabolites are still in your system. It is possible that niacin disrupted neurobiological homeostasis and that some unwanted effects continue to linger after niacin has been eliminated from your plasma.
To help others get a better understanding of your situation, mention the type of niacin you were taking, the dosage, how long you had been taking it, as well as whether you took any other medications along with it. Realize that in most cases, niacin itself should be out of your system in less than 24 hours, and its metabolites should be eliminated from your plasma in under 48 hours. There’s really no reason to suspect that niacin (or metabolites) will remain in circulation for more than 2 days.