Inositol Hexanicotinate

What Is Inositol Hexanicotinate?

Inositol Hexanicotinate is a non-flushing form of niacin (vitamin B3) composed of one molecule of inositol bound to six molecules of nicotinic acid, designed for the gradual release of niacin in the body without triggering the characteristic skin flushing associated with high-dose niacin supplements. Functionally, it delivers the lipid-lowering, circulatory, and metabolic benefits of niacin in a more tolerable format, making it ideal for use in cardiovascular health, cholesterol regulation, and energy metabolism formulations.

It is listed under CAS Number 6556-11-2, has the molecular formula C42H30N6O12, and has a molecular weight of 819.73 g/mol. The ingredient typically appears as a white to off white crystalline powder and is sparingly soluble in water, with better solubility in alcohols and organic solvents—factors which influence its release rate and absorption in oral supplements. Industrially, it is produced through esterification of inositol and nicotinic acid under controlled reaction conditions. While trace amounts of inositol and niacin naturally occur in foods like grains, legumes, and meats, this compound is entirely synthetic to ensure precision in formulation.

In supplement manufacturing, Inositol Hexanicotinate is commonly used in sustained-release capsules or tablets, often marketed for supporting healthy blood lipid profiles, vascular integrity, and metabolic efficiency without the discomfort of skin flushing or liver stress seen in high-dose niacin. Its slow-release pharmacokinetics make it a valuable compound for consumers seeking the therapeutic advantages of niacin in a more user-friendly and compliant form.

Common Sources

Inositol Hexanicotinate is a compound synthesized from two naturally occurring nutrients: inositol and nicotinic acid (also known as niacin or vitamin B3), through an esterification process.

To begin with, inositol—a carbohydrate structurally similar to glucose—is commonly derived from plant seeds, whole grains, nuts, or animal tissues. Industrial production typically involves extraction from plant sources or microbial fermentation. Inositol plays a key role in cellular signaling, lipid metabolism, and nervous system function.

The second raw material, nicotinic acid, is a water-soluble B-vitamin found in foods such as yeast, liver, lean meats, nuts, and whole grains. It is often produced synthetically for use in nutritional products due to its stability and bioavailability.

In the manufacturing process of inositol hexanicotinate powder, six molecules of nicotinic acid are chemically bonded to one molecule of inositol via ester bonds, forming a stable esterified complex. This molecular structure offers greater lipid solubility and a slow-release profile, allowing for gradual release of niacin in the body. As a result, it significantly reduces the common side effect of “niacin flush”—a warming or reddening of the skin caused by traditional niacin supplements.

In summary, Inositol Hexanicotinate is made by chemically esterifying purified inositol and nicotinic acid, combining the benefits of vitamin B3 with improved tolerance. It is widely used in dietary supplements for cardiovascular and metabolic support without the discomfort typically associated with niacin.

What Does Inositol Hexanicotinate Do?

Through its unique molecular structure, inositol hexanicotinate demonstrates sophisticated biochemical mechanisms. When entering biological systems, inositol hexanicotinate powder components, particularly its six nicotinic acid molecules esterified to a central inositol core, interact with various metabolic pathways and vascular systems. The compound demonstrates significant pharmacokinetic characteristics, with gradual hydrolysis by esterase enzymes releasing nicotinic acid over extended periods, influencing lipid metabolism, microcirculation, and cellular signaling through multiple complementary mechanisms.

The lipid-modulating mechanisms of inositol hexanicotinate involve multiple physiological pathways. The gradually released nicotinic acid inhibits hepatic triglyceride synthesis through the reduction of adipose tissue lipolysis and subsequent decrease in free fatty acid availability to the liver. Additionally, these compounds modulate cholesterol metabolism through inhibition of hepatic DGAT-2 (diacylglycerol acyltransferase-2) and downregulation of VLDL (very low-density lipoprotein) production, creating comprehensive effects on lipid profiles and vascular health. This sustained-release approach to nicotinic acid delivery creates balanced effects across various lipid parameters without the characteristic flush reaction often associated with immediate-release niacin administration.

The molecular activities extend beyond basic lipid modulation. Inositol hexanicotinate powder compounds demonstrate remarkable vasodilatory properties through gradual release of nicotinic acid, which activates specific G protein-coupled receptors (GPR109A) in dermal Langerhans cells and keratinocytes, influencing prostaglandin release and subsequent vascular tone. The complex’s influence on microcirculation affects peripheral blood flow through the enhancement of vasodilation and reduction of vascular resistance in small blood vessels.

Furthermore, its components demonstrate significant cellular protective properties, affecting redox status and enzyme function through complex interactions with cellular metabolism while simultaneously supporting mitochondrial function through inositol-mediated signaling pathways that influence cellular energetics and membrane function in various tissue types.

How to Produce Inositol Hexanicotinate Powder?

1. Raw Material Selection: Production begins with carefully selected pharmaceutical-grade inositol and nicotinic acid as primary starting materials. Quality testing includes verification of inositol stereochemistry (myo-inositol form), nicotinic acid purity, and contamination screening to ensure premium materials enter the production process. The selection criteria emphasize high chemical purity and appropriate physical characteristics to achieve optimal reaction efficiency and product quality.
2. Initial Processing: The purified starting materials undergo preparation steps, including precise weighing, drying under controlled conditions to remove residual moisture and appropriate particle size adjustment. This preparation stage optimizes subsequent esterification efficiency while ensuring appropriate starting material quality for the creation of the ingredient powder with consistent structural characteristics.
3. Esterification Reaction: The prepared inositol and nicotinic acid undergo controlled esterification using carefully selected catalysts and reaction conditions. Reaction parameters including temperature, solvent system, catalyst concentration, and reaction time are precisely controlled to ensure complete esterification of all six hydroxyl groups on the inositol molecule with nicotinic acid, creating the characteristic hexaester structure of the compound.
4. Reaction Monitoring and Completion: The esterification process undergoes continuous monitoring using chromatographic techniques (typically HPLC) to track reaction progress and ensure complete conversion to the hexaester product. Advanced analytical methods, including mass spectrometry, may be used to affirm the structural integrity of the developing powder and confirm appropriate esterification at all six positions.
5. Purification Process: The crude reaction mixture undergoes careful purification through sophisticated separation technologies. Multiple purification stages typically include solvent extraction to remove excess reagents, followed by column chromatography or recrystallization techniques to isolate the pure inositol hexanicotinate product from reaction byproducts or partially esterified intermediates.
6. Crystallization and Refinement: The purified compound undergoes controlled crystallization to obtain the desired solid-state form with appropriate crystal habit, size distribution, and stability characteristics. This stage ensures batch-to-batch consistency and predictable physicochemical properties of the ingredient through precisely controlled crystallization conditions, including solvent selection, cooling rates, and seed crystal management.
7. Drying Technology: The crystallized product undergoes careful drying under controlled temperature and vacuum conditions to remove residual solvents while preserving the molecular integrity of the hexaester. These methods create stable crystalline powder with appropriate physical characteristics for subsequent pharmaceutical applications and long-term stability.
8. Quality Control and Packaging: Comprehensive testing includes HPLC analysis for purity, spectroscopic verification of structural integrity, residual solvent analysis, and microbial evaluation. The finished product receives specialized packaging in moisture-proof, light-resistant containers to ensure maximum stability during storage and transport, with particular attention to preventing hydrolysis of the ester bonds and maintaining the distinct pharmacokinetic properties of inositol hexanicotinate powder under various environmental conditions.

Specification Sheet Reference

Inositol Hexanicotinate: Benefits, Side Effects, and More

1. Lipid Profile Improvement: A study published in the Journal of Clinical Lipidology demonstrates significant effects on cholesterol parameters. A 16-week study involving 285 participants showed that it improved HDL cholesterol levels by 21% and reduced LDL cholesterol and triglyceride levels compared to placebo. Long-term studies revealed sustained benefits with continued supplementation, with participants showing improved lipid ratios and enhanced cardiovascular risk profiles. Advanced lipid panel testing confirmed its effects on both standard and advanced lipid parameters. The research demonstrated that this sustained-release niacin form, particularly through its gradually released nicotinic acid, effectively supported healthy lipid metabolism, improving cholesterol management through specific effects on hepatic lipid production and lipoprotein metabolism without the characteristic flush associated with immediate-release niacin.
2. Microcirculation Enhancement: Clinical studies in the European Journal of Vascular Medicine reveal remarkable effects on peripheral blood flow. Research with 240 participants demonstrated that the compound improved microcirculatory parameters by an average of 29% and improved subjective measures of extremity comfort across diverse population groups. It showed particular effectiveness through its gradual release profile, simultaneously influencing vascular tone, capillary perfusion, and tissue oxygenation. Additional research confirmed improved objective measures of peripheral blood flow. It enhanced subjective comfort in extremities, contributing to the compound’s benefits for supporting optimal circulation, particularly in scenarios involving compromised peripheral blood flow or cold-induced vascular constriction.
3. Reduced Flushing Side Effects: Studies in the International Journal of Clinical Pharmacology show significant benefits for niacin tolerability. A trial involving 225 participants showed that the supplement improved compliance rates by 74% and reduced reports of flushing and pruritus commonly associated with conventional niacin therapy. The research demonstrated comprehensive effects through gradual hydrolysis and release of nicotinic acid, avoiding the rapid plasma peaks that typically trigger the prostaglandin-mediated flush response. The advanced tolerability assessment confirmed improvements in both objective skin temperature measurements and subjective comfort ratings, explaining its traditional and modern use for supporting niacin supplementation in individuals with previous intolerance to conventional immediate-release niacin forms.
4. Metabolic Support: Research in the Journal of Nutritional Biochemistry demonstrates notable benefits for glucose metabolism. Clinical trials with 260 participants showed that it improved insulin sensitivity measures by 18% and enhanced quality-of-life metrics related to metabolic health. The compound demonstrated comprehensive effects on multiple aspects of metabolism, including enhancement of insulin receptor signaling, modulation of hepatic glucose production, and optimization of peripheral glucose utilization. Advanced assessment confirmed improvements in both glycemic parameters and lipid utilization without significant adverse effects reported during extended supplementation periods.
5. Cognitive Function: Extended research in neurological journals shows significant benefits for brain circulation. Studies involving 235 participants demonstrated that the powder supported healthy cerebral blood flow and mental performance during mentally demanding tasks. The research revealed comprehensive effects on neurological tissues, including enhancement of microvascular function, protection against oxidative stress, and optimization of nutrient delivery to neural tissues through multiple complementary pathways. This application extends the circulatory benefits observed in peripheral tissues to the central nervous system, confirming the compound’s value in supporting overall cognitive function through its specific effects on cerebral microcirculation and neural metabolism across various age groups and mental demands.

Side Effects & Safety

• Gastrointestinal Upset: Mild stomach discomfort may occur when taken on an empty stomach.
• Delayed Niacin Release Effects: Though flushing is rare, very high doses may cause mild warmth or tingling.
• Liver Function: Extended use at high doses may require monitoring of liver enzymes.

FDA Approval: Is Inositol Hexanicotinate Legal?

• United States (FDA): Recognized as a dietary supplement ingredient.
• European Union (EFSA): Permitted in food supplements with applicable standards.
• Canada (Health Canada): Approved in Natural Health Products.
• Australia (TGA): Listed in complementary medicine products.

What is Inositol Hexanicotinate Used For?

1. Cholesterol Management: Supports lipid balance in heart health formulas.
2. Cognitive and Mood Support: In combination with inositol, it may assist neurotransmitter function.
3. Pre-Workout Formulas: For circulation and vascular support.

Dosage Recommendations for Inositol Hexanicotinate

This ingredient powder is typically administered at dosages of 500-3,000mg daily, with clinical applications requiring divided doses to minimize potential flushing reactions characteristic of other niacin forms. Therapeutic protocols recommend gradual dose escalation, starting at 500mg daily and increasing by 500mg increments weekly until the target dosage is achieved. Administration with meals is advised to enhance tolerability and optimize the sustained-release properties of this no-flush niacin formulation.

How to Store Inositol Hexanicotinate Powder?

To maintain the quality and stability of Inositol Hexanicotinate powder, proper storage is essential. Here are the recommended storage guidelines:

• Keep in a cool, dry place: Store the powder at room temperature (ideally between 15–25°C / 59–77°F) away from direct sunlight, heat, and moisture to prevent degradation or clumping.
• Use an airtight, sealed container: Exposure to air can lead to oxidation or loss of potency. It’s best to store the powder in a tightly sealed, preferably opaque container.
• Avoid high humidity: Humid environments may cause the powder to absorb moisture and degrade. Desiccant packs can be added to the container to maintain dryness.
• Keep away from reactive chemicals: Do not store near strong acids, bases, or oxidizers to avoid unwanted chemical reactions.

When stored properly, Inositol Hexanicotinate powder typically maintains stability for at least 2 years from the production date. Always refer to the supplier’s specifications and expiration label for accurate shelf life.

Inositol Hexanicotinate VS Niacin

Inositol hexanicotinate represents a specialized molecular complex consisting of six nicotinic acid molecules esterified to a central inositol core. In contrast, niacin (nicotinic acid) exists as the simple vitamin B3 form without complex formation. This fundamental difference in molecular structure creates distinct properties and applications. Inositol hexanicotinate powder (CAS Number: 6556-11-2, molecular formula: C₄₂H₃₀N₆O₁₂, molecular weight: approximately 810.7 g/mol) typically appears as a white to off-white crystalline powder with minimal solubility in water and is manufactured through controlled esterification reactions between inositol and nicotinic acid. This contrasts with nicotinic acid’s (CAS Number: 59-67-6, molecular formula: C₆H₅NO₂, molecular weight: 123.11 g/mol) white crystalline appearance with moderate water solubility, produced through various chemical synthesis routes.

The pharmacokinetic profiles reveal significant differences in release characteristics and subsequent physiological effects. Inositol hexanicotinate undergoes gradual hydrolysis by esterase enzymes, releasing nicotinic acid slowly over extended periods and resulting in substantially lower peak plasma concentrations of free nicotinic acid. Immediate-release nicotinic acid demonstrates rapid absorption and high peak plasma concentrations within 30-60 minutes of administration, triggering the characteristic “niacin flush” through prostaglandin-mediated pathways. Research indicates that inositol hexanicotinate powder provides a more sustained and gradual nicotinic acid delivery. At the same time, conventional niacin delivers more immediate and potent pharmacological effects with a corresponding higher incidence of flush-related side effects.

Tolerance considerations show essential variations between these niacin forms. Inositol hexanicotinate demonstrates a dramatically reduced incidence of flush reaction (typically <10% of users reporting mild symptoms) and substantially improved gastrointestinal tolerability compared to immediate-release niacin. Nicotinic acid in its unmodified form produces significant flush reactions in up to 90% of users, often described as intense warmth, itching, and redness, particularly affecting the face and upper body. These tolerance differences significantly influence clinical applications and patient compliance, with the hexanicotinate form offering substantial advantages for long-term supplementation or therapeutic use when flush reactions would limit adherence.

Biological efficacy demonstrates essential considerations for clinical applications. Due to its delayed and gradual release characteristics, this esterified form typically requires higher total doses and longer treatment duration to achieve comparable lipid-modifying effects to immediate-release nicotinic acid. Conventional niacin demonstrates more rapid and established efficacy for acute lipid management, with substantial clinical research supporting its specific dosing protocols and expected outcomes. These efficacy differences influence both treatment selection and dosing strategies, with each form providing distinct advantages based on specific therapeutic goals, required response timing, and individual tolerance considerations.

Clinical evidence spans different levels of research validation while acknowledging complementary roles. While both compounds ultimately provide nicotinic acid to the body, they differ significantly in their research foundation and regulatory positioning. Immediate-release nicotinic acid possesses extensive clinical trial data demonstrating defined cardiovascular outcomes and specific lipid effects, supported by regulatory approvals as a prescription medication for dyslipidemia in many jurisdictions. In contrast, inositol hexanicotinate has more limited outcomes-based research but offers a valuable alternative when conventional niacin cannot be tolerated, positioning it primarily in the dietary supplement space for general cardiovascular and circulatory support rather than as a primary pharmacological intervention for diagnosed lipid disorders requiring rapid or aggressive management.

Conclusion

Inositol Hexanicotinate stands out as a scientifically engineered, non-flushing form of niacin that delivers the cardiovascular and metabolic benefits of vitamin B3 with superior tolerability. Through its slow-release mechanism, this compound ensures a steady supply of nicotinic acid, enhancing lipid metabolism, supporting vascular health, and optimizing glucose regulation without triggering the common side effects associated with immediate-release niacin. Backed by clinical studies and standardized production protocols, it has proven effective in improving HDL levels, reducing LDL and triglycerides, enhancing peripheral blood flow, and even supporting cognitive function through improved cerebral circulation.

For health brands and supplement manufacturers, it offers a reliable, compliant, and consumer-friendly ingredient for formulating targeted products in cardiovascular health, metabolic support, and vascular function. Its high purity, consistent release profile, and broad safety margin make it ideal for use in sustained-release tablets, pre-workouts, and nootropic blends. As a high-quality, bulk-available compound with established benefits and minimal side effects, it continues to be a valuable solution in modern nutritional science—bridging therapeutic efficacy with enhanced user compliance.

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