Niacin (vitamin B3) is an essential vitamin that, at doses about 100 times the daily requirement, works as a cholesterol drug: it raises HDL, lowers LDL and triglycerides, and is one of the few drugs that lowers lipoprotein(a). Two large outcome trials, AIM-HIGH and HPS2-THRIVE, found that adding niacin to statin therapy did not prevent heart attacks or strokes and caused more diabetes, bleeding, infection and other serious side effects. In 2016 the FDA withdrew approval of niacin–statin combination pills for that reason.
People who use anabolic steroids sometimes take niacin because steroids can drive HDL very low. Niacin does raise HDL, but raising HDL has not been shown to protect the heart, and no trial has tested niacin in steroid users. Sustained-release niacin can cause severe liver injury, and a 2024 study linked a niacin breakdown product, 4PY, to vascular inflammation and cardiovascular events.
This page summarizes what the FDA label, the NIH Office of Dietary Supplements, the outcome trials and meta-analyses report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Water-soluble B vitamin; at high doses, a lipid-modifying drug |
| Forms | Nicotinic acid (the lipid-active form); nicotinamide (niacinamide, no lipid effect); inositol hexanicotinate (“no-flush,” poorly absorbed) |
| RDA (adults) | 16 mg niacin equivalents (NE)/day for men, 14 mg NE for women |
| Upper limit (UL) | 35 mg/day from supplements and fortified foods, set to avoid flushing; does not apply under medical supervision |
| Prescription product | Niacin extended-release tablets (Niaspan and generics), US approval 1997; 500 mg and 1,000 mg |
| Labeled dose | Start 500 mg at bedtime; increase by no more than 500 mg every 4 weeks; maintenance 1,000–2,000 mg once daily; over 2,000 mg not recommended |
| Lipid effects (label, 2,000 mg) | LDL −14%, HDL +22%, triglycerides −28%, apolipoprotein B −16% |
| Outcome trials | AIM-HIGH (3,414 patients) and HPS2-THRIVE (25,673): no reduction in cardiovascular events on top of statins |
| Main risks | Flushing (up to 88%), liver injury (especially sustained-release), higher blood sugar and new diabetes, muscle injury with statins, gout, bleeding |
| Half-life | Not stated on the label; first-pass metabolism is extensive and saturable; peak level ≈5 h after extended-release |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Niacin is the name for nicotinic acid and nicotinamide, two forms of vitamin B3 that the body converts into NAD, a coenzyme used in hundreds of energy reactions. The body can also make niacin from the amino acid tryptophan: 60 mg of tryptophan counts as 1 mg of niacin, which is why requirements are given in “niacin equivalents” (NIH ODS). Severe deficiency causes pellagra, but deficiency is rare in the US. Average adult intake from food is about 31 mg/day in men and 21 mg/day in women.
The distinction between forms matters for anyone taking niacin for lipids:
| Form | Lipid effect | Flushing | Notes |
|---|---|---|---|
| Nicotinic acid, immediate-release (“crystalline”) | Yes | Common | Effective; frequent flushing |
| Nicotinic acid, extended-release (prescription) | Yes | Fewer episodes | FDA-approved formulation; dosed once at bedtime |
| Nicotinic acid, sustained-release / timed-release (supplements) | Yes | Less | Linked to severe liver injury (see below) |
| Nicotinamide (niacinamide) | None | No | Does not bind the receptor that mediates niacin’s lipid effects |
| Inositol hexanicotinate (“no-flush”) | Not established | No | Absorption about 30% lower than nicotinic acid on average |
Sources: NIH ODS; niacin ER label.
The ODS also notes that nicotinamide riboside and nicotinamide mononucleotide are related NAD precursors sold as supplements, but they are not marketed or labeled as niacin sources. See NMN, NR and NAD+.
How it works
The label states that niacin’s lipid mechanism “has not been well defined.” It may partly inhibit the release of free fatty acids from fat tissue, increase lipoprotein lipase activity and lower the liver’s production of VLDL and LDL (niacin ER label).
Nicotinic acid binds a receptor called GPR109A (also HCA2) on fat cells, which mediates its anti-lipolytic effect. The same receptor on immune cells in the skin causes flushing: mice lacking GPR109A did not flush, and flushing depended on release of prostaglandins D2 and E2 through the enzyme cyclooxygenase-1 (Benyó et al., J Clin Invest 2005). This is why aspirin, a cyclooxygenase inhibitor, reduces flushing.
Pharmacokinetics
From the extended-release label (niacin ER label):
- Absorption: first-pass metabolism is extensive and saturable, so blood levels are dose-dependent and highly variable. Peak levels occur about 5 hours after an extended-release dose.
- Metabolism: one pathway conjugates niacin with glycine to form nicotinuric acid; the other forms NAD. Excess is methylated in the liver to N1-methylnicotinamide and pyridone products, including 2PY and 4PY (NIH ODS).
- Excretion: 60–76% of an extended-release dose is recovered in urine as niacin and metabolites.
- Sex: plasma levels are generally higher in women, and women may respond at lower doses.
- Formulations are not interchangeable. The label warns against substituting extended-release niacin for equal doses of immediate-release or sustained-release niacin.
Approved medical use
Current label
Prescription extended-release niacin is approved, as an add-on to diet, to lower total cholesterol, LDL, apolipoprotein B and triglycerides and raise HDL in primary hyperlipidemia and mixed dyslipidemia. It is also labeled to reduce recurrent nonfatal heart attacks in people with prior heart attack, to slow atherosclerosis when combined with a bile acid resin, and for severe hypertriglyceridemia. The label carries a limitation of use: adding niacin did not reduce cardiovascular illness or death in statin-treated patients in AIM-HIGH (niacin ER label).
Lipid changes in two 16-week placebo-controlled label trials:
| Daily dose | Total cholesterol | LDL | HDL | Triglycerides | Apo B |
|---|---|---|---|---|---|
| 1,000 mg (n = 41) | −3% | −5% | +18% | −21% | −6% |
| 1,500 mg (n = 76) | −8% | −12% | +20% | −13% | −12% |
| 2,000 mg (n = 41) | −10% | −14% | +22% | −28% | −16% |
| Placebo | 0 to +2% | −1 to +1% | +2 to +4% | 0 to +12% | +1% |
Across older studies, pharmacologic doses raise HDL by 10–30% and lower LDL by 10–25%, triglycerides by 20–50% and lipoprotein(a) by 10–30% (NIH ODS).
Combination pills withdrawn
On April 18, 2016, the FDA withdrew approval of Advicor (extended-release niacin with lovastatin, approved 2001) and Simcor (extended-release niacin with simvastatin, approved 2008). The agency concluded that the totality of evidence “no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events” (Federal Register, 2016).
In Europe, niacin combined with laropiprant (Tredaptive, Pelzont, Trevaclyn), a drug added to block flushing, was suspended in January 2013 after the HPS2-THRIVE results; the European Commission’s binding decision followed on March 22, 2013 (EMA).
What the research shows
The early evidence: Coronary Drug Project
In the Coronary Drug Project, completed in 1975, men aged 30–64 with prior heart attack took niacin or placebo. Over 5 years, nonfatal repeat heart attacks were 8.9% on niacin vs 12.2% on placebo, while total mortality did not differ (24.4% vs 25.4%). At 15 years, deaths were lower in the former niacin group (52.0% vs 58.2%), but this was not an original endpoint and patients had been off niacin for about 9 years (niacin ER label). This trial predates statins.
Modern outcome trials on top of statins
| Trial | Patients | Treatment | HDL / LDL change | Primary outcome | Key harms |
|---|---|---|---|---|---|
| AIM-HIGH (AIM-HIGH Investigators, NEJM 2011) | 3,414 with cardiovascular disease, low HDL, LDL 40–80 mg/dL on simvastatin ± ezetimibe | Extended-release niacin 1,500–2,000 mg/day vs placebo; stopped early at mean 3 years for futility | HDL 35 → 42 mg/dL; LDL 74 → 62 mg/dL; triglycerides 164 → 122 mg/dL (2 years) | 16.4% vs 16.2%; HR 1.02 (95% CI 0.87–1.21) | Ischemic stroke 1.6% vs 0.9% (HR 1.79, 95% CI 0.95–3.36, not significant); more “blood glucose increased” and diabetes |
| HPS2-THRIVE (HPS2-THRIVE Collaborative Group, NEJM 2014) | 25,673 with vascular disease on statin-based therapy | Extended-release niacin 2 g + laropiprant 40 mg vs placebo; median 3.9 years | LDL 10 mg/dL lower; HDL 6 mg/dL higher vs placebo | Major vascular events 13.2% vs 13.7%; rate ratio 0.96 (95% CI 0.90–1.03) | Excess serious diabetes complications (+3.7 points), new diabetes (+1.3), gastrointestinal (+1.0), musculoskeletal (+0.7), skin (+0.3), infection (+1.4), bleeding (+0.7) |
AIM-HIGH’s placebo contained 100–150 mg of immediate-release niacin to mimic flushing (niacin ER label). A detailed HPS2-THRIVE safety analysis found hazard ratios of 1.32 for new diabetes, 1.38 for serious bleeding and 1.22 for serious infection, with the excess risks largest in the first year (Haynes et al., Clin Ther 2019).
Pooled evidence
A Cochrane review of 23 randomized trials (39,195 participants, median dose 2 g/day) found that niacin did not reduce overall mortality (RR 1.05, 95% CI 0.97–1.12, high-quality evidence), cardiovascular mortality, heart attacks (RR 0.93, 95% CI 0.87–1.00) or strokes. Participants on niacin were about twice as likely to stop treatment because of side effects (RR 2.17). The authors concluded that cardiovascular benefits “are unlikely” (Schandelmaier et al., Cochrane 2017).
The American College of Cardiology and American Heart Association do not recommend niacin as an add-on to statins, while noting it may be useful in some cases of severe hypertriglyceridemia (NIH ODS).
Why raising HDL did not help
The failure of niacin fits genetic evidence. In a Mendelian randomization study (using inherited gene variants as a natural experiment), people carrying an endothelial lipase variant that raises HDL by 0.14 mmol/L were predicted to have 13% fewer heart attacks but had the same risk as non-carriers (OR 0.99, 95% CI 0.88–1.11). A genetic score that raised HDL also showed no protection, while a score that raised LDL increased risk as expected (Voight et al., Lancet 2012). A higher HDL number, by itself, does not reliably mean lower risk.
Lipoprotein(a)
Lipoprotein(a), or Lp(a), is a largely inherited, LDL-like particle that raises cardiovascular risk. Niacin is one of the few available drugs that lowers it:
- A meta-analysis of 14 placebo-controlled trials (9,013 subjects) found extended-release niacin lowered Lp(a) by 22.9% (95% CI 18.5–27.3%), with similar effects below and above 2,000 mg/day (Sahebkar et al., Metabolism 2016).
- A 2025 meta-analysis of 147 trials found niacin lowered Lp(a) by 7.1 mg/dL (a 37% reduction from baseline), alongside PCSK9 antibodies, inclisiran and CETP inhibitors; statins, ezetimibe, omega-3s and fibrates did not lower it. The authors noted it is unknown whether this translates into fewer events (Xie et al., Atherosclerosis 2025).
Neither AIM-HIGH nor HPS2-THRIVE showed a benefit despite these effects.
The 4PY finding
In 2024, researchers analyzed blood from stable cardiac patients and found that the terminal breakdown products of excess niacin, 2PY and 4PY, predicted major adverse cardiovascular events over 3 years. In two validation cohorts, the adjusted hazard ratios for 4PY were 1.89 (US, n = 2,331) and 1.99 (Europe, n = 832). A gene variant that raised 2PY and 4PY was associated with higher levels of soluble VCAM-1, an adhesion molecule that recruits white blood cells to vessel walls. In mice, physiological levels of 4PY (but not 2PY) increased VCAM-1 expression and leukocyte adhesion to blood vessels (Ferrell et al., Nat Med 2024).
What this does and does not show:
- It is association data in humans plus a mechanism in mice. It does not prove that niacin intake causes heart disease.
- It offers one possible explanation for why niacin improved lipids yet failed to reduce events.
- The study did not test niacin supplements or define a safe intake.
Relevance to anabolic steroid use
AAS can lower HDL far more than ordinary dyslipidemia does. In strength athletes self-administering AAS, HDL fell from about 42 to 17 mg/dL and apolipoprotein B rose (Hartgens et al., Br J Sports Med 2004). In a prospective cohort of 100 men, LDL rose by about 17 mg/dL and HDL fell by about 15 mg/dL during a cycle, returning to baseline within 3 months after stopping (Smit et al., Andrologia 2022).
Points that matter for this group:
- No trial has tested niacin in AAS users. Whether it raises steroid-suppressed HDL, and whether that would mean anything for risk, is unknown.
- HDL raising has not prevented events in any modern niacin trial, and genetic data argue against the HDL number as a target.
- Lp(a) already falls during AAS use in both studies above (−37.6% in the cohort), so niacin’s Lp(a) effect is less relevant during a cycle.
- Overlapping side effects. Niacin can raise blood sugar, uric acid and liver enzymes. Oral 17α-methylated steroids such as oxymetholone carry their own liver warnings, so combining them with high-dose niacin stacks liver risks that have never been studied together.
- LDL and apolipoprotein B have the strongest outcome evidence. See atorvastatin, rosuvastatin, ezetimibe and evolocumab.
Side effects and risks
Flushing
Flushing (warmth, redness, itching or tingling of the face, arms and chest) was reported by up to 88% of patients in extended-release trials, and 6% stopped because of it. At 1,500 mg/day, immediate-release niacin caused about 8.6 flushing episodes per patient per month vs 1.9 for extended-release. Rare flushing reactions include dizziness, fast heartbeat and fainting. The label says flushing may be reduced by taking aspirin (up to 325 mg) 30 minutes beforehand, increasing the dose slowly, taking niacin with food and avoiding alcohol, hot drinks and spicy foods around the dose (niacin ER label). Doses of 30–50 mg or more of nicotinic acid typically cause flushing (NIH ODS).
Liver toxicity, especially sustained-release
The clearest evidence comes from a 1994 double-blind trial in 46 adults that raised immediate-release or sustained-release niacin from 500 to 3,000 mg/day in 6-week steps. None of the 23 immediate-release patients developed liver toxicity, but 12 of 23 (52%) on sustained-release niacin did. 78% of the sustained-release group withdrew before reaching 3,000 mg, often because of gastrointestinal symptoms, fatigue and rising liver enzymes. The authors concluded that “the SR form of niacin is hepatotoxic and should be restricted from use” (McKenney et al., JAMA 1994).
The prescription label warns of severe liver toxicity, including fulminant hepatic necrosis, when sustained-release products were substituted for immediate-release niacin at equal doses. It is contraindicated in active liver disease and requires liver tests before treatment, every 6–12 weeks in the first year and about every 6 months after. In its own trials (245 patients, mean 17 weeks), no patient with normal baseline values rose above 3 times the upper limit of normal (niacin ER label). Many over-the-counter “slow-release” supplements are sustained-release products.
Blood sugar and diabetes
Niacin can worsen insulin resistance and raise glucose, most often at 1.5 g/day or more (NIH ODS). In HPS2-THRIVE, new diabetes rose by 32% and serious diabetes complications by 56% in people who already had diabetes (Haynes et al., 2019).
Other effects
From the label and the ODS fact sheet:
- Muscle injury: rhabdomyolysis with lipid-altering doses (1 g/day or more) combined with statins, especially in older adults and people with diabetes, kidney failure or untreated hypothyroidism. AIM-HIGH had 4 cases on niacin vs 1 on placebo.
- Uric acid and gout: elevated uric acid; caution if prone to gout.
- Blood tests: small dose-related drops in platelet count (mean −11% at 2,000 mg) and phosphorus (−13%), and a small rise in prothrombin time (about +4%).
- Gastrointestinal: nausea, heartburn, abdominal pain; active peptic ulcer and arterial bleeding are contraindications.
- Eyes: blurred vision and macular edema (fluid in the center of the retina).
- Low blood pressure severe enough to increase falls.
Misuse to “beat” drug tests
Niacin is promoted online for clearing drugs before urine tests. An emergency medicine report described 4 cases, 2 with life-threatening effects including liver toxicity, metabolic acidosis and low then high blood sugar (Mittal et al., Ann Emerg Med 2007).
Interactions
| Drug | Concern |
|---|---|
| Statins | Higher risk of myopathy and rhabdomyolysis |
| Diabetes medicines | Niacin can raise glucose; monitoring and dose changes may be needed |
| Anticoagulants and antiplatelet drugs | Lower platelets and longer prothrombin time; HPS2-THRIVE showed excess bleeding |
| Nitrates, calcium channel blockers, adrenergic blockers | Caution in unstable angina or acute heart attack |
| Isoniazid and pyrazinamide | Interfere with niacin production from tryptophan |
| Alcohol | Worse flushing; caution with heavy drinking because of liver risk |
Sources: niacin ER label; NIH ODS.
Legal status and use in sport
Niacin is a prescription drug in its extended-release lipid-lowering form and a dietary supplement at lower doses in the US. It is not named on the WADA 2026 Prohibited List. Aspirin, often taken with niacin to reduce flushing, is also permitted; see low-dose aspirin.
Key takeaways
- A vitamin at drug doses. Lipid effects need about 1,000–2,000 mg/day of nicotinic acid, roughly 100 times the RDA; nicotinamide has no lipid effect.
- Good lipid numbers, no outcome benefit. Niacin raises HDL by about 20%, lowers LDL, triglycerides and Lp(a), yet AIM-HIGH and HPS2-THRIVE found no reduction in cardiovascular events on top of statins.
- Real harms. HPS2-THRIVE showed more new diabetes, bleeding, infection and gastrointestinal, muscle and skin problems; the FDA withdrew niacin–statin pills in 2016.
- Sustained-release niacin can injure the liver. In a head-to-head trial, 52% on sustained-release developed liver toxicity vs none on immediate-release.
- 4PY is a new concern. A 2024 study linked a niacin breakdown product to vascular inflammation and cardiovascular events; this is association data, not proof of harm.
- Untested in steroid users. AAS suppress HDL, but no trial shows that niacin offsets this or lowers risk; LDL and apo B are the better-supported targets.
Sources
- Amneal Pharmaceuticals. Niacin extended-release tablets prescribing information. 2026. DailyMed.
- NIH Office of Dietary Supplements. Niacin: fact sheet for health professionals. Accessed November 2026. ODS.
- US Food and Drug Administration. AbbVie Inc.; withdrawal of approval of new drug applications for ADVICOR and SIMCOR. Federal Register. 2016;81:22608–22609. Federal Register.
- European Medicines Agency. Tredaptive, Pelzont and Trevaclyn: referral (suspension of marketing authorisations). 2013. EMA.
- AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–2267. PubMed.
- HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–212. PubMed.
- Haynes R, Valdes-Marquez E, Hopewell JC, et al. Serious adverse effects of extended-release niacin/laropiprant: results from the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial. Clin Ther. 2019;41(9):1767–1777. PubMed.
- Schandelmaier S, Briel M, Saccilotto R, et al. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2017;6(6):CD009744. PubMed.
- Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572–580. PubMed.
- Sahebkar A, Reiner Ž, Simental-Mendía LE, et al. Effect of extended-release niacin on plasma lipoprotein(a) levels: a systematic review and meta-analysis of randomized placebo-controlled trials. Metabolism. 2016;65(11):1664–1678. PubMed.
- Xie S, Galimberti F, Olmastroni E, et al. Effect of lipid-lowering therapies on lipoprotein(a) levels: a comprehensive meta-analysis of randomized controlled trials. Atherosclerosis. 2025;408:120420. PubMed.
- Ferrell M, Wang Z, Anderson JT, et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat Med. 2024;30(2):424–434. PubMed.
- Benyó Z, Gille A, Kero J, et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005;115(12):3634–3640. PubMed.
- McKenney JM, Proctor JD, Harris S, et al. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA. 1994;271(9):672–677. PubMed.
- Mittal MK, Florin T, Perrone J, et al. Toxicity from the use of niacin to beat urine drug screening. Ann Emerg Med. 2007;50(5):587–590. PubMed.
- Hartgens F, Rietjens G, Keizer HA, et al. Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). Br J Sports Med. 2004;38(3):253–259. PubMed.
- Smit DL, Grefhorst A, Buijs MM, et al. Prospective study on blood pressure, lipid metabolism and erythrocytosis during and after androgen abuse. Andrologia. 2022;54(4):e14372. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List (in effect January 1, 2026). 2025. WADA.