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Inositol hexanicotinate (also known as inositol hexaniacinate or inositol nicotinate) is the hexanicotinic acid ester of meso-inositol. This chemical compound consists of six molecules of nicotinic acid (niacin) with an inositol molecule in the center of the structure.
It is a popular form of food supplements where it acts a source of niacin (vitamin B3), one of the essential human nutrients. Although the inositol hexanicotinate complex does not represent an essential nutrient, niacin is pivotal to cellular metabolism, playing the important role in coenzyme function and oxidation-reduction reactions.
Inositol hexanicotinate is (at least partially) absorbed intact and subsequently hydrolysed in the body, resulting in a free nicotinic acid and inositol. Although gastrointestinal absorption of inositol hexanicotinate can vary significantly, approximately 70% of an orally ingested dose absorbs into the bloodstream.
Oral administration of inositol hexanicotinate results in a steady increase in the level of free nicotinic acid in blood and plasma. The compound appears to be metabolized slowly, with serum levels of nicotinic acid peaking roughly 6-10 hours after ingestion, compared to the intake of free nicotinic acid when plasma levels can peak after merely half an hour.
The extent of hydrolysis of inositol hexanicotinate appears to be very low; therefore, differences in plasma levels of free nicotinic acid after administering similar oral doses of inositol hexanicotinate and free nicotinic acid may be responsible for different effects observed in clinical studies. In fact, the observed effects for inositol hexanicotinate may not be related to its total nicotinic acid content, but rather to a direct effect of the compound on the organism.
Beneficial effects of free nicotinic acid and extended-release nicotinic acid in lowering the concentration of lipids are well established, but the beneficial effects of inositol hexanicotinate on serum lipids depends on the uptake and subsequent release of the nicotinic acid moieties from the inositol hexanicotinate molecule. Considering the aforementioned low extent of hydrolysis, this mechanism is not sufficient to significantly alter plasma lipid profiles.
Inositol hexanicotinate has a proven beneficial effect on enothelium-dependent vasodilatation (widening of blood vessels), thus it improves blood flow in conditions where it is compromised. In Europe it is often prescribes as a patented drug known under a name Hexopal, indicated for the symptomatic relief of Raynaud’s phenomenon and severe intermittent claudication. A common dose of inositol hexanicotinate for these conditions is 3 g per day, which can be increased to 4 g per day if necessary.
Nicotinic acid given as inositol hexanicotinate in a dose of 10 mg per day would amount to a daily dose of 11 mg inositol hexanicotinate, with the release of 2.4 mg inositol upon hydrolysis. Since the estimated normal dietary intake of inositol amounts up to 1500 mg of myoinositol (naturally occuring inositol) per day, the European Food Safety Authority panel concluded that the intake of 2.4 mg inositol/day, resulting from the abovementioned dose of 11 mg per day, would not be of safety concern.
Inositol hexanicotinate acts as a slow-release supply of nicotinic acid; hence the flushing effect is not a likely event when inositol hexanicotinate is used as a source of niacin due to the slow hydrolysis of the nicotinic acid molecules from the inositol. For that reason this compound is often described as “no flush niacin”. No adverse effects have been observed in clinical trials using inositol hexanicotinate up to 4000 mg daily for 3 months.
Even though there are no genotoxicity data available on inositol hexanicotinate, there are no safety concerns. As already mentioned, inositol hexanicotinate is hydrolysed to inositol and nicotinic acid, which are both endogenous compounds that occur in several dietary products. In addition, the safety of nicotinic acid has been thoroughly evaluated by various authorities – including the Scientific Committee on Food (SCF).