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inositol hexanicotinate

Also known as: IHN, no-flush niacin, inositol nicotinate, hexanicotinoyl inositol, Inositol hexanicotinate

Overview

Inositol hexanicotinate (IHN) is a synthetic chemical compound formed by esterifying six molecules of nicotinic acid (niacin) with one molecule of inositol. It is primarily known as "no-flush niacin" due to its design to slowly release nicotinic acid, thereby reducing the common flushing side effect associated with immediate-release niacin. IHN is used as a nutritional supplement, mainly for managing dyslipidemia (abnormal blood lipids), improving peripheral circulation, and potentially aiding in blood pressure regulation. While it offers a gentler alternative to traditional niacin, research indicates that its slower release also results in lower plasma levels of free nicotinic acid, which may impact its overall efficacy compared to direct niacin. The evidence base for IHN's specific benefits is mixed, with more robust data existing for inositol and niacin separately.

Benefits

Inositol hexanicotinate (IHN) offers several potential benefits, though the strength of evidence varies. A 2021 meta-analysis of inositol supplementation (not exclusively IHN) showed significant reductions in systolic blood pressure (approx. 5.7 mmHg) and diastolic blood pressure (approx. 7.1 mmHg), particularly in metabolic syndrome patients at doses around 4000 mg for over 8 weeks. This suggests a potential indirect benefit for blood pressure through its inositol component. Another meta-analysis indicated that inositol supplementation generally reduces triglycerides and may improve lipid profiles in metabolic disease patients. However, IHN's specific effects on lipids are less clear, as it produces much lower plasma nicotinic acid levels compared to direct niacin, which may lead to weaker lipid-lowering effects. Some older studies suggest IHN might improve symptoms of intermittent claudication (poor circulation), but high-quality, recent randomized controlled trial (RCT) data are limited. While inositol derivatives have been explored for dermatological and neurological conditions, these benefits are not well-established for IHN specifically.

How it works

Inositol hexanicotinate (IHN) functions by slowly hydrolyzing in the body, releasing nicotinic acid and inositol. The released nicotinic acid then acts primarily via GPR109A receptors, also known as niacin receptors. This interaction leads to vasodilation, which is the widening of blood vessels, and modulates lipid metabolism. Specifically, nicotinic acid reduces the hepatic synthesis of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol, while simultaneously increasing high-density lipoprotein (HDL) cholesterol. The slow release of nicotinic acid from IHN results in lower peak plasma concentrations compared to immediate-release niacin, which accounts for the reduced flushing side effect but may also limit its overall efficacy in significantly altering lipid profiles. Inositol, the other component, has its own mechanisms, including involvement in cell signaling and osmotic regulation, which contribute to its observed effects on blood pressure and triglycerides.

Side effects

Inositol hexanicotinate (IHN) is generally well-tolerated, with a significantly lower incidence of flushing compared to immediate-release niacin. Common side effects, occurring in over 5% of users, are typically mild and include gastrointestinal discomfort and headache. Unlike traditional niacin, severe flushing is rare with IHN. Uncommon side effects, reported in 1-5% of cases, are not well-documented for IHN but may include mild hepatotoxicity or muscle symptoms, though these are rare. Significant hepatotoxicity or myopathy has not been reported in clinical trials at typical doses. Caution is advised regarding potential drug interactions, particularly with other lipid-lowering medications and antidiabetic drugs. IHN is contraindicated in individuals with known hypersensitivity to niacin derivatives. It should be used with caution in patients with pre-existing liver disease or peptic ulcer disease. Data on its safety during pregnancy or lactation are limited, and its use in these populations is not well-studied.

Dosage

The typical dosage range for Inositol hexanicotinate (IHN) in clinical studies is approximately 1500 mg to 4000 mg per day. This dosage is often divided and taken orally with meals to minimize potential gastrointestinal discomfort. While a minimum effective dose is not definitively established, studies on inositol derivatives frequently use doses around 1000–4000 mg/day. The maximum safe dose for IHN is not well-established, but doses up to 4000 mg/day have generally appeared safe in trials. Due to its slow hydrolysis and lower peak plasma nicotinic acid levels, extended-release formulations of IHN are common to help maintain consistent levels and further reduce flushing. There are no specific cofactors required for IHN absorption or efficacy, though general B-vitamin status may play a role in overall metabolic health.

FAQs

Does IHN cause flushing?

IHN causes significantly less flushing than immediate-release niacin because it releases nicotinic acid slowly into the bloodstream.

Is IHN effective for cholesterol?

Evidence for IHN's direct lipid-lowering effects is weaker than for niacin, as its lower plasma nicotinic acid levels may limit significant improvements in lipid profiles.

Can IHN lower blood pressure?

Some research on inositol supplementation suggests it can reduce blood pressure, but specific data on IHN's direct impact on blood pressure are limited.

How long does it take to see effects from IHN?

Potential benefits on blood pressure or lipids, if any, may take 8 weeks or more of consistent supplementation to become noticeable.

Is IHN safer than niacin?

Generally, yes. IHN is considered safer than immediate-release niacin due to fewer flushing episodes and a lower risk of hepatotoxicity at typical doses.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/34330516/ – This systematic review and meta-analysis of randomized controlled trials (RCTs) investigated the effect of inositol supplementation on blood pressure. It found that inositol significantly reduced both systolic and diastolic blood pressure, particularly in patients with metabolic syndrome, at doses around 4000 mg for durations exceeding 8 weeks. The study highlights inositol's potential as a therapeutic agent for blood pressure management, though it included various forms of inositol, not exclusively IHN.
https://www.crnusa.org/sites/default/files/files/resources/13-CRNVMS3-NIACIN.pdf – This document provides an overview of niacin and its derivatives, including inositol hexanicotinate (IHN). It discusses the pharmacokinetic differences between IHN and immediate-release niacin, noting that IHN produces much lower plasma nicotinic acid levels. This explains the reduced flushing but also suggests potentially weaker lipid-modifying effects compared to direct niacin. It references older studies, like Harthon & Brattsand (1979), which provided early insights into IHN's bioavailability and minimal lipid effects.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5968598/ – This meta-analysis of RCTs examined the effects of inositol supplementation on lipid profiles in patients with metabolic diseases. It concluded that inositol significantly reduced triglyceride levels, although its effects on other lipid parameters were mixed. The study supports the general lipid-modulating benefits of inositol, but it's important to note that it encompassed various inositol forms, and publication bias was detected for some lipid outcomes.
https://www.jintegrativederm.org/api/v1/articles/122716-inositol-for-treating-dermatological-disorders-a-systematic-review.pdf – This systematic review explored the use of inositol for treating dermatological disorders. While it discusses the potential benefits of inositol derivatives in skin conditions, the evidence specifically for inositol hexanicotinate (IHN) in this context is limited and not well-established. The review broadly covers the role of inositol in cellular processes relevant to skin health.
https://orda.shef.ac.uk/articles/poster/A_systematic_review_and_meta_analysis_of_the_clinical_effectiveness_of_cilostazol_naftidrofuryl_oxalate_pentoxifylline_and_inositol_nicotinate_for_symptom_management_of_intermittent_claudication_2012_/11913363 – This systematic review and meta-analysis investigated the clinical effectiveness of various drugs, including inositol nicotinate, for managing symptoms of intermittent claudication. It suggested some benefit of inositol nicotinate on symptoms, but highlighted that the evidence was limited by a small number of high-quality randomized controlled trials and small sample sizes. This indicates low to moderate quality evidence for this specific application of IHN.