Inositol Hexanicotinate (IHN)

Evidence Level
Preliminary
2 Clinical Trials
4 Documented Benefits
1/5 Evidence Score

Inositol hexanicotinate (IHN), also known as inositol hexaniacinate or sold as 'no-flush niacin', is a compound consisting of six niacin molecules ester-linked to a single inositol molecule. It was developed in mid-20th-century Europe (where it is marketed as Hexopal) and was hoped to offer the cardiovascular and lipid effects of immediate-release niacin without the characteristic skin-flushing reaction. That hope did not hold up. In the one head-to-head trial cited here, a blinded, placebo-controlled study of 120 adults with mild to moderate dyslipidemia (40 per group) taking 1,500 mg a day for 6 weeks, IHN produced no significant improvement in cholesterol or any other lipid measure, no different from placebo, and it showed no evidence of bioavailability, meaning the researchers found no sign it was absorbed and released as niacin. The wax-matrix extended-release niacin arm of the same trial did work (total cholesterol down 11 percent, LDL down 18 percent, non-HDL down 15 percent, HDL up 12 percent). So the product most often bought for cholesterol did nothing to cholesterol in its own key trial.

Studied Dose 1,500 mg/day was the dose tested in the only lipid trial cited here, and it produced no lipid effect and no evidence of absorption; label doses of 500-1,000 mg/day are common but have not been shown to do anything.
Active Compound Inositol hexanicotinate (six nicotinic acid molecules ester-linked to myo-inositol).

Benefits

Niacin-Form Marketed as Flush-Free

IHN is sold as a niacin supplement that avoids the warm flushing reaction caused by immediate-release nicotinic acid. It does avoid the flush, but the likely reason is that very little niacin is being released: in the trial cited here, IHN showed no evidence of bioavailability and behaved like placebo on every lipid measure. Skipping the flush is not the same as getting niacin's effects.

Studied in People Diagnosed With Raynaud's Disease (One 1988 Trial)

IHN has been sold in Europe under the brand name Hexopal, and one double-blind, placebo-controlled trial from 1988 tested it in people already diagnosed with primary Raynaud's disease, a circulatory condition that makes fingers go cold and white. That single, nearly 40-year-old study in patients is the only trial of this use cited here. It has not been replicated in the evidence on this page, and it does not show what IHN does for circulation in a healthy person.

Not a Reliable Source of Usable Niacin

On paper the molecule is built from inositol plus six niacin units. But the trial cited here found no evidence that the niacin is actually released and absorbed, so IHN should not be counted on as a source of usable niacin. If you want niacin, a plain niacin or niacinamide product is the studied option.

Reported Mild Tolerability

In the 6-week trial of 120 adults, IHN at 1,500 mg a day was well tolerated, with side effects similar to placebo. That is easy to explain: it also performed like placebo on every lipid measure and showed no evidence of being absorbed.

Mechanism of action

1

Slow Ester Hydrolysis (Proposed)

IHN was designed on the assumption that intestinal and tissue esterases would slowly hydrolyze the ester bonds to release nicotinic acid gradually. In practice, the trial cited here reported no evidence of bioavailability at 1,500 mg a day, so that slow release does not appear to happen to any meaningful degree in people.

2

Minimal Nicotinic Acid Bioavailability

The blinded 6-week trial in 120 adults with mild to moderate dyslipidemia reported that IHN showed no evidence of bioavailability. That is the simplest explanation for why IHN changed nothing while the extended-release niacin comparison arm lowered LDL by 18 percent in the same study.

3

Niacinamide Conversion (Proposed, Not Measured)

One proposed explanation is that whatever small amount of niacin is freed gets converted to niacinamide, a form that does not trigger the receptor behind niacin's cholesterol effects. This is a theory put forward to explain the negative result, not something the trials cited here measured.

Clinical trials

1
IHN Was No Better Than Placebo for Lipids, and Showed No Evidence of Absorption

Blinded, placebo-controlled trial in 120 adults with mild to moderate dyslipidemia (40 per arm), 1,500 mg a day for 6 weeks after a 4-week diet lead-in (J Clin Lipidol 2013, PMID 23351578)

120 adults with mild to moderate dyslipidemia, 40 each assigned to wax-matrix extended-release niacin, IHN, or placebo

Wax-matrix extended-release niacin lowered total cholesterol by 11 percent, LDL by 18 percent and non-HDL by 15 percent, and raised HDL by 12 percent (all statistically significant). IHN produced no significant improvement in lipids and was no different from placebo, and the authors reported that it showed no evidence of bioavailability. Their own summary was that IHN was well tolerated but was no better than placebo in lipid improvement and showed no evidence of bioavailability. One more thing worth knowing: in the niacin arm, average liver enzymes rose 24 to 27 percent, which is why niacin at lipid-changing doses is a medical therapy that needs monitoring rather than a product to switch to on your own.

2
Hexopal in Primary Raynaud's Disease

Double-blind, randomized, placebo-controlled trial of IHN (sold as Hexopal) in people diagnosed with primary Raynaud's disease (Clin Rheumatol 1988, PMID 3044673)

People diagnosed with primary Raynaud's disease, a circulatory condition, not healthy adults

This 1988 trial reported some symptom improvement with IHN compared with placebo in people already diagnosed with Raynaud's disease. It is a single, small, nearly 40-year-old study with no replication in the evidence cited here, it measured nothing about cholesterol or circulation in healthy people, and a supplement is not a treatment for Raynaud's disease.

Side effects and drug interactions

Common Potential side effects

Well tolerated at 1,500 mg a day for 6 weeks in the 120-person trial, with side effects similar to placebo.
Mild gastrointestinal upset such as nausea may occur occasionally.
Unlike free niacin, flushing is rare due to limited nicotinic acid release.
Headache reported infrequently at higher doses.
Marketing that presents IHN as equal to niacin for cholesterol is directly contradicted by the trial cited here, in which IHN was no better than placebo and showed no evidence of being absorbed.

Important Drug interactions

Theoretical interactions with lipid-modifying medications, though clinically minor due to low bioavailability.
Cautions borrowed from high-dose niacin, such as use alongside blood thinners like warfarin, are theoretical for IHN because the cited trial found no evidence it releases niacin. Still tell your clinician everything you take.
No interaction studies with blood pressure medicines are cited here, so any concern is theoretical rather than observed.
Discuss with a clinician before using as a replacement for prescription niacin therapy.

Frequently asked questions about Inositol Hexanicotinate (IHN)

What is inositol hexanicotinate (flush-free niacin)?

Inositol hexanicotinate is six niacin molecules chemically attached to one inositol molecule, sold as 'no-flush niacin'. It is marketed to deliver niacin's benefits without the skin flushing, but in the blinded trial cited on this page it did not change cholesterol at all and showed no evidence of being absorbed as niacin.

Does flush-free niacin work as well as regular niacin?

It does avoid the flush. But for cholesterol it is not just 'less effective', it was no better than placebo. In a blinded 6-week trial of 120 adults taking 1,500 mg a day, IHN moved no lipid measure, while the extended-release niacin arm lowered LDL by 18 percent, and the researchers found no evidence IHN was absorbed. Niacin at cholesterol-changing doses is a medical therapy that needs liver monitoring (liver enzymes rose 24 to 27 percent on average in that niacin arm), so it is a conversation with your doctor, not a product swap.

How much inositol hexanicotinate should I take?

Labels commonly suggest 500 to 1,000 mg. Note that the trial cited here used more, 1,500 mg a day for 6 weeks, and still found no lipid effect and no evidence of absorption, so a smaller dose is not going to do more. Follow product labeling, and discuss any high-dose niacin plan with a doctor.

Is inositol hexanicotinate safe?

In the trial cited here it was well tolerated at 1,500 mg a day for 6 weeks, with side effects like placebo. The liver-enzyme concern belongs mainly to real sustained-release niacin (in that same trial, the niacin arm showed average liver enzyme increases of 24 to 27 percent). Do not take high-dose niacin products long-term without medical oversight.

What is Inositol Hexanicotinate?

Inositol hexanicotinate (IHN), also known as inositol hexaniacinate or sold as 'no-flush niacin', is a compound consisting of six niacin molecules ester-linked to a single inositol molecule.

What is Inositol Hexanicotinate used for?

Inositol Hexanicotinate is researched primarily for Cardiovascular. IHN is sold as a niacin supplement that avoids the warm flushing reaction caused by immediate-release nicotinic acid. It does avoid the flush, but the likely reason is that very little niacin is being released: in the trial cited here, IHN…

What is the recommended dosage of Inositol Hexanicotinate?

The clinically studied dose is 1,500 mg/day was the dose tested in the only lipid trial cited here, and it produced no lipid effect and no evidence of absorption; label doses of 500-1,000 mg/day are common but have not been shown to do anything. Always follow the product label and check with a healthcare provider for personal advice.

Is Inositol Hexanicotinate safe, and does it have side effects?

For most healthy adults, Inositol Hexanicotinate is well tolerated at studied doses. Reported effects can include: Well tolerated at 1,500 mg a day for 6 weeks in the 120-person trial, with side effects similar to placebo. Mild gastrointestinal upset such as nausea may occur occasionally. It may also interact with some medications. Inositol Hexanicotinate is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Inositol Hexanicotinate interact with any medications?

Possible interactions include: Theoretical interactions with lipid-modifying medications, though clinically minor due to low bioavailability. Cautions borrowed from high-dose niacin, such as use alongside blood thinners like warfarin, are theoretical for IHN because the cited trial found no evidence it release… If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Inositol Hexanicotinate?

NutraSmarts rates the evidence for Inositol Hexanicotinate as Preliminary (1 out of 5). It is backed by 2 clinical trials and 2 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(2 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Keenan JM. Wax-matrix extended-release niacin vs inositol hexanicotinate: a comparison of wax-matrix, extended-release niacin to inositol hexanicotinate 'no-flush' niacin in persons with mild to moderate dyslipidemia. Journal of Clinical Lipidology. 2013;J Clin Lipidol. 2013 Jan-Feb;7(1):14-23..PubMedUsed to support: Blinded, placebo-controlled trial in 120 adults with mild to moderate dyslipidemia (40 per arm), 1,500 mg a day for 6 weeks after a 4-week diet lead-in. IHN gave no significant improvement in lipids, matching placebo, and showed no evidence of bioavailability. Wax-matrix extended-release niacin lowered total cholesterol 11 percent, LDL 18 percent and non-HDL 15 percent and raised HDL 12 percent, with average liver enzyme increases of 24 to 27 percent.
  2. Sunderland GT, Belch JJ, Sturrock RD, Forbes CD, McKay AJ. A double blind randomised placebo controlled trial of hexopal in primary Raynaud's disease. Clinical Rheumatology. 1988;Clin Rheumatol. 1988 Mar;7(1):46-9..PubMedUsed to support: Single 1988 double-blind, placebo-controlled trial of IHN (Hexopal) in people diagnosed with primary Raynaud's disease, reporting modest symptom effects. This is a disease-population study, not evidence of lipid benefit or of any circulatory benefit in healthy people, and it is not replicated in the evidence cited here.