Olbetam; 5-methylpyrazine-2-carboxylic acid 4-oxide; CAS 51037-30-0; ATC C10AD06 · Evidence-based safety and harm-reduction overview.
| Also known as | Olbetam; 5-methylpyrazine-2-carboxylic acid 4-oxide; CAS 51037-30-0; ATC C10AD06 |
| Category | Supplement |
| CAS Number | 51037-30-0 |
| PubChem CID | 5310993 |
| Molecular Formula | C6H6N2O3 |
| ATC Code | C10AD06 (antilipolytic agent) |
| HSL inhibition duration | Approximately 9-12 hours (vs. ~3 hours for nicotinic acid) |
| Elimination | Exclusively renal; no significant hepatic metabolism; 100% oral bioavailability reported |
| US legal status | Not approved by the US FDA for any medical indication. Acipimox is an established prescription pharmaceutical in parts of Europe (marketed as Olbetam), but holds no approved status in the United States. Sourced domestically only through specialty chemical suppliers for laboratory research purposes; not for human consumption under US law. |
Acipimox is a synthetic niacin analog and antilipolytic agent with lipid-modifying properties. It inhibits hormone-sensitive lipase (HSL) in adipose tissue, thereby suppressing the breakdown of stored triglycerides into free fatty acids and secondarily reducing hepatic VLDL synthesis. It was developed as a longer-acting, better-tolerated alternative to nicotinic acid for the treatment of dyslipidemia and has been clinically used in Europe since the 1980s. More recent investigational interest has centered on its potential effects on mitochondrial function, skeletal muscle energy metabolism, and NAD-related pathways in aging and mitochondrial disease populations.
Acipimox acts primarily as an inhibitor of hormone-sensitive lipase (HSL) in adipose tissue, an enzyme responsible for hydrolyzing stored triglycerides into free fatty acids and glycerol. By suppressing this lipolytic flux, it reduces the supply of free fatty acids to the liver, which secondarily lowers hepatic VLDL synthesis and plasma triglyceride and LDL levels while modestly raising HDL. It is also a weak agonist at GPR109A (nicotinic acid receptor 1, also known as HCA2), the G-protein coupled receptor implicated in both the lipid-modifying and flushing effects of niacin, though its binding affinity at GPR109A is in the micromolar range. Its longer duration of antilipolytic action relative to nicotinic acid (approximately 9-12 hours) is attributed to pharmacokinetic differences rather than fundamentally distinct receptor pharmacology. Separately, interest in mitochondrial disease applications is based on the hypothesis that reducing fatty acid oxidative flux may relieve substrate bottlenecks in patients with impaired mitochondrial respiratory chain function, and potentially influence NAD metabolism in skeletal muscle; this mechanistic rationale remains under active investigation.
Acipimox was developed in the late 1970s and early 1980s as a structural analog of nicotinic acid intended to retain lipid-modifying efficacy while reducing the prominent flushing and hepatotoxicity associated with high-dose niacin therapy. It entered European clinical use under the brand name Olbetam, achieving approval for the treatment of hyperlipoproteinemia types II and IV. Clinical use in lipidology declined substantially with the dominance of statin therapy from the 1990s onward. Beginning in the 2010s, researchers began investigating acipimox in novel metabolic contexts, particularly mitochondrial myopathy and age-related sarcopenia, driven by mechanistic hypotheses regarding fatty acid flux, NAD homeostasis, and skeletal muscle bioenergetics. It has never been approved by the US FDA.
Acipimox has the strongest evidence base in its historical role as a lipid-lowering agent. Multiple multicenter randomized trials conducted in the 1980s and 1990s established its efficacy in reducing LDL cholesterol and triglycerides and raising HDL in patients with type II and IV hyperlipoproteinemia, with a well-characterized safety record from this era. More recent clinical interest has pivoted toward metabolic and mitochondrial applications. The AIMM trial (ISRCTN 12895613; EudraCT 2018-002721-29), a randomized double-blind placebo-controlled study in mitochondrial myopathy patients, has been registered and its protocol published (2022); it targets ATP restoration in skeletal muscle as the primary endpoint and was ongoing as of available data. A separate feasibility RCT in older adults with sarcopenia (ISRCTN 87404878, published GeroScience, March 2025) evaluated acipimox effects on muscle NAD levels, mitochondrial function, and physical performance; the compound was well-tolerated but did not improve primary outcomes. These newer studies are small or feasibility-grade and should not be interpreted as establishing efficacy in these newer indications. No large confirmatory trials in mitochondrial disease or sarcopenia have been completed to date per available records.
Published European clinical use for dyslipidemia has involved oral doses in the range of 250 mg two to three times daily, with the total daily dose varying by indication and renal function in the historical literature. Feasibility and investigational studies in sarcopenia and mitochondrial myopathy have used comparable oral dosing schedules. These ranges are reported here as literature context only and do not constitute a dosing protocol or clinical recommendation. Appropriate dosing for any indication is a medical decision requiring clinician oversight, renal function assessment, and evaluation of contraindications.
This is general research/context information, not medical advice or a recommended protocol.
No established evidence-based stacking protocols exist for acipimox in the research chemical or investigational context. In historical dyslipidemia management it was sometimes used alongside dietary intervention and occasionally other lipid agents. Combination with statins was not a primary use case given its distinct mechanism. Investigational mitochondrial disease protocols have not established combination regimens. No stacking guidance can be responsibly offered outside a supervised clinical trial or physician-directed treatment plan.
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Get tested with Ulta Lab Tests →No. Acipimox is not approved by the US FDA for any medical indication. It is available as a prescription pharmaceutical in some European markets under the brand name Olbetam but has no approved status in the US.
No dosing guidance can be provided here. Acipimox is a pharmacologically active compound with contraindications, renal dosing requirements, and meaningful drug interactions. Any use in a clinical or investigational context requires evaluation by a qualified clinician.
Acipimox and nicotinic acid (niacin) share the antilipolytic mechanism via HSL inhibition and weak GPR109A agonism, but acipimox produces a longer duration of effect (approximately 9-12 hours vs. approximately 3 hours), is associated with substantially less flushing at therapeutic doses, and lacks the hepatotoxicity concern associated with high-dose extended-release niacin. However, neither has the cardiovascular outcomes evidence base supporting statin therapy.
As of available data, no. The AIMM trial in mitochondrial myopathy was still ongoing when its protocol was published in 2022, and results have not been publicly reported in the sources reviewed. A feasibility RCT in older adults with sarcopenia published in GeroScience in March 2025 found acipimox was well-tolerated but did not improve primary outcomes. These are early-stage or feasibility studies; efficacy in these indications is not established.
Flushing is the most frequent adverse effect and can be partially reduced by taking low-dose aspirin 20-30 minutes before each dose. Gastrointestinal side effects occur. High doses may worsen gout. It is contraindicated in peptic ulcer disease, recent myocardial infarction, acute heart failure, active bleeding, and severe renal impairment. Dose reduction is required in renal insufficiency given exclusive renal elimination.
The mechanistic hypothesis is that in patients with impaired mitochondrial respiratory chain function, reducing free fatty acid availability via HSL inhibition may relieve oxidative stress and substrate overload in affected muscle mitochondria, and may also influence cellular NAD metabolism. This rationale is biologically plausible but remains investigational and has not been confirmed in adequately powered clinical trials.
Medical & legal disclaimer. This site is for informational and harm-reduction purposes only. It is not medical advice and is not a substitute for a licensed healthcare professional. The compounds discussed are largely not approved by the FDA for human use and many are sold strictly as research chemicals 'not for human consumption.' Nothing here is an endorsement to purchase, possess, or use any substance. Laws vary by jurisdiction. Always consult a qualified physician and follow the law where you live.
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